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Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial.

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

Abstract

Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have suggested that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (N = 45) and patients with treatment-resistant depression (N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (N = 35) when compared to placebo (N = 34). Furthermore, at D2 just patients treated with ayahuasca (N = 14), and not with placebo (N = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).

Almeida, R. N., Galvão, A. C. D. M., Da Silva, F. S., Silva, E. A. D. S., Palhano-Fontes, F., Maia-de-Oliveira, J. P., … & Galvão-Coelho, N. (2019). Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca: observation from a randomized controlled trial. Frontiers in psychology, 10, 1234., https://doi.org/10.3389/fpsyg.2019.01234
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Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers

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

Abstract

BACKGROUND:

Numerous anecdotal reports suggest that repeated use of very low doses of lysergic acid diethylamide (LSD), known as microdosing, improves mood and cognitive function. These effects are consistent both with the known actions of LSD on serotonin receptors and with limited evidence that higher doses of LSD (100-200 μg) positively bias emotion processing. Yet, the effects of such subthreshold doses of LSD have not been tested in a controlled laboratory setting. As a first step, we examined the effects of single very low doses of LSD (0-26 μg) on mood and behavior in healthy volunteers under double-blind conditions.

METHODS:

Healthy young adults (N = 20) attended 4 laboratory sessions during which they received 0 (placebo), 6.5, 13, or 26 μg of LSD in randomized order at 1-week intervals. During expected peak drug effect, they completed mood questionnaires and behavioral tasks assessing emotion processing and cognition. Cardiovascular measures and body temperature were also assessed.

RESULTS:

LSD produced dose-related subjective effects across the 3 doses (6.5, 13, and 26 μg). At the highest dose, the drug also increased ratings of vigor and slightly decreased positivity ratings of images with positive emotional content. Other mood measures, cognition, and physiological measures were unaffected.

CONCLUSIONS:

Single microdoses of LSD produced orderly dose-related subjective effects in healthy volunteers. These findings indicate that a threshold dose of 13 μg of LSD might be used safely in an investigation of repeated administrations. It remains to be determined whether the drug improves mood or cognition in individuals with symptoms of depression.

Bershad, A. K., Schepers, S. T., Bremmer, M. P., Lee, R., & de Wit, H. (2019). Acute subjective and behavioral effects of microdoses of LSD in healthy human volunteers. Biological Psychiatry., 10.1016/j.biopsych.2019.05.019
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‘Never drop without your significant other, cause that way lies ruin’: The boundary work of couples who use MDMA together.

/ MDMA, Papers, Psychology, Publications / / , ,

Abstract

MDMA has a variety of pro-social effects, such as increased friendliness and heightened empathy, yet there is a distinct lack of research examining how these effects might intertwine with a romantic relationship. This article seeks to compensate for this absence and explore heterosexual couples’ use of MDMA through the lens of the boundaries they construct around these experiences. Three couple interviews, two diary interviews and eight written diaries about couples’ MDMA practices were analysed. Douglas’ (2001) and Stenner’s (2013) work around order, disorder and what lies at the threshold between the two are employed here. This conceptual approach allows us to see what happens at the border of MDMA experiences as crucial to their constitution. Two main themes are identified in the data. First, MDMA use was boundaried from daily life both temporally and corporeally: the drug was tied to particular times in people’s lives as well as the performance of rituals which engaged the material world and reenchanted everyday spaces and selves. Secondly, other people are excluded from MDMA experiences to varying degrees in order to preserve the emotionally intense space for the couple alone. This paper claims that MDMA use forms part of a spectrum of relationship ‘work’ practices; a unique kind of ‘date night’ that revitalises couples’ connection. Hence, MDMA should be recognised as transforming couple as well as individual practices. Finally, it is suggested that harm reduction initiatives could distinguish more ‘messy’ forms of emotional harm and engage with users’ language of ‘specialness’ to limit negative impacts of MDMA use.
Anderson, K., Reavey, P., & Boden, Z. (2019). ‘Never drop without your significant other, cause that way lies ruin’: The boundary work of couples who use MDMA together. International Journal of Drug Policy, 71, 10-18., https://doi.org/10.1016/j.drugpo.2019.05.004
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Psychedelic drugs-a new era in 
psychiatry?


/ Anxiety Disorders / PTSD, Depressive Disorders, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / /

Abstract

This article covers the renaissance of classical psychedelic drugs such as psilocybin and LSD plus 3,4-methylene dioxymethamphetamine (MDMA-ecstasy) in psychiatric research. These drugs were used quite extensively before they became prohibited. This ban had little impact on recreational use, but effectively stopped research and clinical treatments, which up to that point had looked very promising in several areas of psychiatry. In the past decade a number of groups have been working to re-evaluate the utility of these substances in medicine. So far highly promising preliminary data have been produced with psilocybin in anxiety, depression, smoking, alcoholism, and with MDMA for post-traumatic stress disorder (PTSD) and alcoholism. These findings have led to the European Medicines Agency approving psilocybin for a phase 3 study in treatment-resistant depression and the Food and Drug Administration for PTSD with MDMA. Both trials should read out in 2020, and if the results are positive we are likely to see these medicines approved for clinical practice soon afterwards.

Nutt, D. (2019). Psychedelic drugs—a new era in psychiatry?. Dialogues in clinical neuroscience, 21(2), 139., https://dx.doi.org/10.31887%2FDCNS.2019.21.2%2Fdnutt
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Psychedelic drugs-a new era in 
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Motives and side-effects of microdosing with psychedelics among users

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

Abstract

BACKGROUND:

Microdosing with psychedelics has gained considerable media attention where it is portrayed as a performance enhancer, especially popular on the work floor. While reports are in general positive, scientific evidence about potential negative effects is lacking aside from the prevalence and motives for use. The present study addressed this gap by surveying psychedelic users about their experience with microdosing including their dosing schedule, motivation, and potential experienced negative effects.

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, and had experience with microdosing were included in the analyses.

RESULTS:

In total, 1116 of the respondents were either currently microdosing (79.5%) or microdosed in the past (20.5%). Lysergic acid diethylamide (10 mcg) and psilocybin (0.5 g) were the most commonly used psychedelics with a microdosing frequency between 2 and 4 times per week. The majority of users, however, were oblivious about the consumed dose. Performance enhancement was the main motive to microdose (37%). The most reported negative effects were of psychological nature and occurred acutely while under the influence.

CONCLUSION:

In line with media reports and anecdotes, the majority of our respondents microdosed to enhance performance. Negative effects occurred mostly acutely after substance consumption. However, the main reason to have stopped microdosing was that it was not effective. Future experimental placebo-controlled studies are needed to test whether performance enhancement can be quantified and to assess potential negative effects after longer term microdosing.

Hutten, N. R., Mason, N. L., Dolder, P. C., & Kuypers, K. P. (2019). Motives and side-effects of microdosing with psychedelics among users. International Journal of Neuropsychopharmacology., 10.1093/ijnp/pyz029

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Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin

/ Mushrooms / Psilocybin, Neuroscience, Papers, Publications / / , , , , , ,

Abstract

Growing evidence from the dynamical analysis of functional neuroimaging data suggests that brain function can be understood as the exploration of a repertoire of metastable connectivity patterns (‘functional brain networks’), which potentially underlie different mental processes. The present study characterizes how the brain’s dynamical exploration of resting-state networks is rapidly modulated by intravenous infusion of psilocybin, a tryptamine psychedelic found in “magic mushrooms”. We employed a data-driven approach to characterize recurrent functional connectivity patterns by focusing on the leading eigenvector of BOLD phase coherence at single-TR resolution. Recurrent BOLD phase-locking patterns (PL states) were assessed and statistically compared pre- and post-infusion of psilocybin in terms of their probability of occurrence and transition profiles. Results were validated using a placebo session. Recurrent BOLD PL states revealed high spatial overlap with canonical resting-state networks. Notably, a PL state forming a frontoparietal subsystem was strongly destabilized after psilocybin injection, with a concomitant increase in the probability of occurrence of another PL state characterized by global BOLD phase coherence. These findings provide evidence of network-specific neuromodulation by psilocybin and represent one of the first attempts at bridging molecular pharmacodynamics and whole-brain network dynamics.

Lord, L. D., Expert, P., Atasoy, S., Roseman, L., Rapuano, K., Lambiotte, R., … & Cabral, J. (2019). Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin. NeuroImage, 199, 127-142., 10.1016/j.neuroimage.2019.05.060

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Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat.

/ Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , , , , , ,

Abstract

OBJECTIVE:
Psilocybin is a serotonin receptor agonist with a therapeutic potential for treatment-resistant depression and other psychiatric illnesses. We investigated whether the administration of psilocybin had an antidepressant-like effect in a rat model of depression.
METHODS:
Using the Flinders Sensitive Line (FSL) rat model of depression, we assessed the antidepressant-like effect of psilocin and psilocybin, measured as a reduction in immobility time in the forced swim test (FST). We measured locomotor activity in an open field test (OFT) to control for stimulant properties of the drugs. We performed a set of experiments to test different doses, treatment paradigms, and timing of the tests in relation to the drug administration.
RESULTS:
Psilocin and psilocybin showed no effect on immobility, struggling, or swimming behaviour in the FST and no effect on locomotor activity in the OFT. FSL rats did show significantly more immobility than their control strain, the Flinders Resistant Line, as expected.
CONCLUSION:
Psilocin and psilocybin showed no antidepressant-like effect in the FSL rats, despite a positive effect in humans. This suggests that other animal models of depression and other behavioural tests may be more appropriate for translational studies in the effects of psilocybin.
Jefsen, O., Højgaard, K., Christiansen, S. L., Elfving, B., Nutt, D. J., Wegener, G., & Müller, H. K. (2019). Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat. Acta neuropsychiatrica, 1-7., https://doi.org/10.1017/neu.2019.15
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N,N-dimethyltryptamine Prevents Renal Ischemia-Reperfusion Injury in a Rat Model

/ DMT, Papers, Psychiatry & Medicine, Publications / / , , , , , ,

Abstract

BACKGROUND:

Ischemia reperfusion (I/R) injury remains one of the most challenging fields of organ transplantation. It is highly associated with the use of expanded criteria donors that might conclude to delayed graft function or early or late graft failure.

OBJECTIVE:

To investigate the metabolic, microcirculatory parameters, and histologic changes under the effect of N,N-dimethyltryptamine (DMT) in a renal I/R model in rats.

METHOD:

In 26 anesthetized rats both kidneys were exposed. In the control group (n = 6) no other intervention happened. In 20 other animals, the right renal vessels were ligated, and after 60 minutes the right kidney was removed. The left renal vessels were clamped for 60 minutes then released, followed by 120 minutes of reperfusion. In the I/R group (n = 10), there was no additive treatment, while in I/R + DMT group (n = 10) DMT was administered 15 minutes before ischemia. Blood samples were taken, laser Doppler measurement was performed, and both kidneys were evaluated histologically.

RESULTS:

Microcirculation (blood flux units [BFU]) diminished in all groups, but remarkably so in the I/R + DMT group. This group compensated better after the 30th minute of reperfusion. The control and I/R + DMT groups had similar BFUs after 120 minutes of reperfusion, but in the I/R group BFU was higher. Tubular necrosis developed in the I/R and I/R + DMT groups too; it was moderated under DMT effect, and severe without. Histologic injuries were less in I/R + DMT Group compared to non-treated animals.

CONCLUSION:

Histologic changes characteristic to I/R injuries were reversible and microcirculation recovered at the end of 120 minutes reperfusion under the administration of DMT. DMT can be used for renoprotection in kidney transplantation.

Nemes, B., Pető, K., Németh, N., Mester, A., Magyar, Z., Ghanem, S., … & Bidiga, L. (2019, May). N, N-dimethyltryptamine Prevents Renal Ischemia-Reperfusion Injury in a Rat Model. In Transplantation proceedings (Vol. 51, No. 4, pp. 1268-1275). Elsevier. 10.1016/j.transproceed.2019.04.005
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Cessation and reduction in alcohol consumption and misuse after psychedelic use

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

Abstract

Background:

Meta-analysis of randomized studies using lysergic acid diethylamide (LSD) for alcohol use disorder (AUD) showed large, significant effects for LSD efficacy compared to control conditions. Clinical studies suggest potential anti-addiction effects of LSD and mechanistically-related classic psychedelics for alcohol and other substance use disorders.

Aims:

To supplement clinical studies, reports of psychedelic use in naturalistic settings can provide further data regarding potential effects of psychedelics on alcohol use.

Methods:

An anonymous online survey of individuals with prior AUD reporting cessation or reduction in alcohol use following psychedelic use in non-clinical settings.

Results:

343 respondents, mostly White (89%), males (78%), in the USA (60%) completed the survey. Participants reported seven years of problematic alcohol use on average before the psychedelic experience to which they attributed reduced alcohol consumption, with 72% meeting retrospective criteria for severe AUD. Most reported taking a moderate or high dose of LSD (38%) or psilocybin (36%), followed by significant reduction in alcohol consumption. After the psychedelic experience 83% no longer met AUD criteria. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced alcohol misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with a greater reduction in alcohol consumption, controlling for prior alcohol consumption and related distress.

Conclusions:

Although results cannot demonstrate causality, they suggest that naturalistic psychedelic use may lead to cessation or reduction in problematic alcohol use, supporting further investigation of psychedelic-assisted treatment for AUD.
Garcia-Romeu, A., Davis, A. K., Erowid, F., Erowid, E., Griffiths, R. R., & Johnson, M. W. (2019). Cessation and reduction in alcohol consumption and misuse after psychedelic use. Journal of Psychopharmacology, 0269881119845793., https://doi.org/10.1177%2F0269881119845793
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MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials.

/ Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / / , , , , , ,

Abstract

BACKGROUND:
Posttraumatic stress disorder is a prevalent mental health condition with substantial impact on daily functioning that lacks sufficient treatment options. Here we evaluate six phase 2 trials in a pooled analysis to determine the study design for phase 3 trials of MDMA-assisted psychotherapy for PTSD.
METHODS:
Six randomized, double-blind, controlled clinical trials at five study sites were conducted from April 2004 to February 2017. Active doses of MDMA (75-125 mg, n = 72) or placebo/control doses (0-40 mg, n = 31) were administered to individuals with PTSD during manualized psychotherapy sessions in two or three 8-h sessions spaced a month apart. Three non-drug 90-min therapy sessions preceded the first MDMA exposure, and three to four followed each experimental session.
RESULTS:
After two blinded experimental sessions, the active group had significantly greater reductions in CAPS-IV total scores from baseline than the control group [MMRM estimated mean difference (SE) between groups - 22.0 (5.17), P < 0.001]. The between-group Cohen’s d effect size was 0.8, indicating a large treatment effect. After two experimental sessions, more participants in the active group (54.2%) did not meet CAPS-IV PTSD diagnostic criteria than the control group (22.6%). Depression symptom improvement on the BDI-II was greatest for the active group compared to the control group, although only trended towards significant group differences [MMRM, estimated mean difference (SE) between groups - 6.0 (3.03), P = 0.053]. All doses of MDMA were well tolerated, with some expected reactions occurring at greater frequency for the active MDMA group during experimental sessions and the 7 days following.
CONCLUSIONS:
MDMA-assisted psychotherapy was efficacious and well tolerated in a large sample of adults with PTSD. These studies supported expansion into phase 3 trials and led to FDA granting Breakthrough Therapy designation for this promising treatment.
Mithoefer, M. C., Feduccia, A. A., Jerome, L., Mithoefer, A., Wagner, M., Walsh, Z., … & Doblin, R. (2019). MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology, 1-11., https://doi.org/10.1007/s00213-019-05249-5
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Psychedelics and Acceptance and Commitment Therapy (ACT): A Process-Based Approach - September 15th

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