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Effects of the hallucinogenic beverage ayahuasca on voluntary ethanol intake by rats and on cFos expression in brain areas relevant to drug addiction

February 6, 2022 / Ayahuasca, Neuroscience, Papers, Substance Use Disorder / Leave a Comment / By / , , , , ,

Abstract

Ayahuasca is a hallucinogenic infusion used in religious rituals that has serotoninergic properties and may be a potential therapeutic option for drug addiction. In this study, Wistar rats had intermittent access to ethanol for 8 weeks, receiving water (control), naltrexone (NTX, 2 mg/kg body weight [bw] intraperitoneally [i.p.]) or ayahuasca (Aya) at 0.5x, 1x, or 2x the ritual dose in the final 5 days. A naïve group had access only to water. Ethanol intake was estimated throughout the experiment, and cFos expression was evaluated in medial orbital cortex (MO), ventral orbital cortex (VO), lateral orbital cortex (LO), nucleus accumbens (NAc), and striatum. Treatment with either NTX or Aya (oral) did not decrease ethanol intake compared to the baseline level (5th to 7th week), but the NTX group intake was significantly lower than controls (p < 0.05). Ethanol significantly increased cFos expression in the MO region for control (p < 0.0001), NTX (p < 0.05), Aya1 (p < 0.001), and Aya2 (p < 0.0001) groups. This increase was also observed in the VO for the Aya1 group (p = 0.035), in the LO for the Aya2 group (p < 0.01), and in NAc for NTX and ayahuasca groups (p < 0.005). Furthermore, NTX and Aya0.5 treatment decreased cFos expression compared to controls in the MO region (p < 0.05 and p < 0.01, respectively), but only the ayahuasca group reached levels not significantly different from the naïve group. Studies using other protocols and dose regime are necessary to better investigate the impact of ayahuasca on alcohol intake by rats to support the observations in humans. Additionally, the role of ayahuasca in mediating cFos expression in other selected brain regions and its relationship with the serotoninergic/dopaminergic systems and drug addiction need further investigation.

Nolli, L. M., de Oliveira, D., Alves, S. S., von Zuben, M. V., Pic-Taylor, A., Mortari, M. R., & Caldas, E. D. (2020). Effects of the hallucinogenic beverage ayahuasca on voluntary ethanol intake by rats and on cFos expression in brain areas relevant to drug addiction. Alcohol (Fayetteville, N.Y.), 84, 67–75. https://doi.org/10.1016/j.alcohol.2019.10.005

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High-dose ketamine infusion for the treatment of posttraumatic stress disorder in combat veterans.

November 1, 2019 / Anxiety Disorders / PTSD, Ketamine, Papers, Psychology, Publications / By / , , ,

Abstract

INTRODUCTION:
Combat veterans are at high risk for the development of posttraumatic stress disorder (PTSD) and substance use disorders. Ketamine has been shown to be an effective treatment for numerous mental health disorders, although research on its efficacy in combat-related PTSD in veterans is very limited.
METHODS:
The study population consisted of 30 US military veterans with combat-related PTSD. Participants underwent a standard induction series of six 1-hour ketamine infusions with the goal of obtaining a transpersonal dissociative experience. Participants were given a series of self-report questionnaires to assess for changes in symptoms of depression, PTSD, and substance use prior to the first and sixth infusions.
RESULTS:
Symptoms of depression as measured by change in score on the Patient Health Questionnaire decreased significantly from an average of 18.9 to 9.5 (P < .001). Similarly, symptoms of PTSD as measured by change in score on the PSTD Checklist for DSM-5 dropped significantly from an average of 56.2 to 31.3 (P < .001). Self-reported levels of substance use did not significantly decrease during the study period, although the level of use trended down.
CONCLUSIONS:
This observational study suggests that high-dose ketamine infusion therapy, which induced a transpersonal dissociative experience, could be a valuable tool in the treatment of combat-related PTSD. Further study is needed to better elucidate ketamine’s mechanism of action with regards to the treatment of PTSD.
Ross, C., Jain, R., Bonnett, C. J., & Wolfson, P. (2019). High-dose ketamine infusion for the treatment of posttraumatic stress disorder in combat veterans. Annals of clinical psychiatry: official journal of the American Academy of Clinical Psychiatrists, 31(4), 271-279., https://www.ncbi.nlm.nih.gov/pubmed/31675388
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Philanthropists Fund Johns Hopkins Center for Study of Psychedelics

October 31, 2019 / Papers, Psychology, Publications / By /

Abstract

Johns Hopkins claims many medical firsts, including the first use of rubber gloves during surgery, the first radical prostatectomy for prostate cancer, the first implant of an automatic defibrillator in a patient.

In September, Hopkins launched what the school believes to be another, more unusual first: the first US Center for Psychedelic and Consciousness Research, funded by $17 million from a private foundation and 4 philanthropists, including author and technology investor Tim Ferriss.

Rubin, R. (2019). Philanthropists Fund Johns Hopkins Center for Study of Psychedelics. Jama, 322(19), 1849-1851., https://dx.doi.org/10.1001/jama.2019.17126
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Serotonergic hallucinogens/psychedelics could be promising treatments for depressive and anxiety disorders in end-stage cancer.

October 28, 2019 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , ,

Abstract

In a recent issue of the BMC Psychiatry, the evidence of effectiveness of treatments for psychiatric conditions in end-stage cancer patients was reviewed (Johnson, 2018). The review was comprehensive, and included traditional and non-traditional/alternative treatments, including herbal medicines and spirituality. However, evidence showing that classic or serotonergic hallucinogens/psychedelics such as psilocybin and lysergic acid diethylamide (LSD) could be effective treatments for depressive and anxiety disorders in end-stage cancer was not included. In this commentary, we expand the information available on the original article by briefly reviewing data from recent placebo-controlled, double-blind, cross-over clinical trials showing evidence that administration of single (or few) doses of LSD and psilocybin was associated with rapid and sustained reductions in depressive and anxiety symptoms in patients with end-stage cancer and other life-threatening diseases (e.g., Bechterew’s disease, Parkinson’s disease, Celiac disease). Since these substances seem to produce rapid and sustained therapeutic effects with single (or few) doses and well tolerated, large-scale, prospective, multi-site studies of end-stage cancer and classical/serotonergic hallucinogens/psychedelics should be performed to improve our understanding of the therapeutic potentials of these drugs and their use on clinical practice.
dos Santos, R. G., Bouso, J. C., & Hallak, J. E. (2019). Serotonergic hallucinogens/psychedelics could be promising treatments for depressive and anxiety disorders in end-stage cancer. BMC psychiatry, 19(1), 321., https://doi.org/10.1186/s12888-019-2288-z
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The ethics of psychedelic research in disorders of consciousness.

October 9, 2019 / Ayahuasca, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , ,

Abstract

This article provides an ethical analysis of psychedelic research involving disorders of consciousness patients. We apply two internationally accepted approaches for analyzing the ethics of human research, the Value-Validity Framework and Component Analysis, to a research program recently proposed by Scott and Carhart-Harris. We focus on Scott and Carhart-Harris’s proposal, but the ethical frameworks outlined are applicable to other novel research protocols in the science of consciousness.
Peterson, A., Tagliazucchi, E., & Weijer, C. (2019). The ethics of psychedelic research in disorders of consciousness. Neuroscience of Consciousness, 2019(1), niz013., https://doi.org/10.1093/nc/niz013
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Acute effects of lysergic acid diethylamide (LSD) on resting brain function.

September 30, 2019 / LSD, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

Lysergic acid diethylamide (LSD) is a potent hallucinogenic substance that was extensively investigated by psychiatrists during the 1950s and 1960s. Researchers were interested in the unique effects induced by this substance, some of which resemble symptoms seen in schizophrenia. Moreover, during that period LSD was studied and used for the treatment of several mental disorders such as depression, anxiety, addiction and personality disorders. Despite this long history of research, how LSD induces its specific effects on a neuronal level has been relatively unclear. In recent years there has been a revival of research in hallucinogenic drugs and their possible clinical applications. These contemporary studies in the UK and Switzerland include neuroimaging studies using functional magnetic resonance imaging (fMRI). In this review, we collect and interpret these recent neuroimaging findings. Overall, previous results across studies indicate that LSD administration is associated with extensive alterations in functional brain connectivity, measuring the correlated activities between different brain regions. The studies mostly reported increases in connectivity between regions and, more specifically, consistently found increased connectivity within the thalamocortical system. These latter observations are in agreement with models proposing that hallucinogenic drugs exert their effects by inhibiting cerebral filtering of external and internal data. However, studies also face several limitations, including potential biases of neuroimaging measurements.
Müller, F., & Borgwardt, S. (2019). Acute effects of lysergic acid diethylamide (LSD) on resting brain function. Swiss Medical Weekly, 149(3940)., https://doi.org/10.4414/smw.2019.20124
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The Psilocybin-Telomere Hypothesis: An Empirically Falsifiable Prediction Concerning the Beneficial Neuropsychopharmacological Effects of Psilocybin on Genetic Aging

September 24, 2019 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By /

Abstract

We introduce a novel hypothesis which states that the therapeutic utilisation of psilocybin has beneficial effects on genetic aging. Ex hypothesi, we predict a priori that controlled psilocybin interventions exert quantifiable positive impact on leucocyte telomere length (telomeres are a robust predictor of mortality and multifarious aging-related diseases). Our hypothesising follows the Popperian logic of scientific discovery, viz., bold (and refutable) conjectures form the very foundation of scientific progress. The ‘psilocybin-telomere hypothesis’ is formalised as a logically valid deductive (syllogistic) argument and we provide substantial evidence to support the underlying premises. Impetus for our theorising derives from a plurality of converging empirical sources indicating that psilocybin has persistent beneficial effects on various aspects of mental health (e.g., in the context of depression, anxiety, PTSD, OCD, addiction, etc.). Additional support is based on a large corpus of studies that establish reliable correlations between mental health and telomere attrition (improved mental health is generally correlated with longer telomeres). Another pertinent component of our argument is based on recent studies which demonstrate that “meditative states of consciousness” provide beneficial effects on genetic aging. Similarly, psilocybin can induce states of consciousness that are neurophysiologically and phenomenologically significantly congruent with meditative states. Furthermore, prior research has demonstrated that a single dose of psilocybin can occasion life-changing transformative experiences (≈ 70% of healthy volunteers rate their experience with psilocybin amongst the five personally most meaningful lifetime events, viz., ranked next to giving birth to a child or losing a loved one). We postulate that these profound psychological events leave quantifiable marks at the molecular genetic/epigenetic level. Given the ubiquitous availability and cost effectiveness of telomere length assays, we suggest that quantitative telomere analysis should be regularly included in future psilocybin studies as an adjunctive biological marker (i.e., to facilitate scientific consilience via methodological triangulation). In order to substantiate the ‘psilocybin-telomere hypothesis’ potential neuropsychopharmacological, endocrinological, and genetic mechanisms of action are discussed (e.g., HPA-axis reactivity, hippocampal neurogenesis, neurotropic growth factors such as BDNF, 5-HT2A receptor agonism, neuroplasticity/synaptoplasticity, brain-wide alterations in neuronal functional connectivity density, involvement of the SLC6A4 serotonin transporter gene, inter alia). The proposed research agenda is thus intrinsically highly interdisciplinary, and it has deep ramifications from a philosophy of science perspective as it connects the epistemic level (qualitative experiential phenomenology) with the ontic level (quantitative molecular genetics) of analysis. In the long term, multidisciplinary and innovative investigations of the ‘psilocybin-telomere hypothesis’ could contribute to the improvement of senotherapeutic psychological interventions and the identification of novel geroprotective and neuroprotective/restorative pharmaceutical targets to decelerate genetic aging and improve well-being and quality of life during the aging process.
Germann, C. B. (2020). The Psilocybin-Telomere Hypothesis: An empirically falsifiable prediction concerning the beneficial neuropsychopharmacological effects of psilocybin on genetic aging. Medical hypotheses, 134, 109406., https://doi.org/10.1016/j.mehy.2019.109406
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The psychedelic renaissance: the next trip for psychiatry?

September 23, 2019 / Depressive Disorders, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By

Abstract

The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland – CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.
Kelly, J. R., Baker, A., Babiker, M., Burke, L., Brennan, C., & O’Keane, V. (2019). The psychedelic renaissance: the next trip for psychiatry?. Irish journal of psychological medicine, 1-5., https://doi.org/10.1017/ipm.2019.39
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