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Psilocybin-assisted therapy for depression: How do we advance the field?

November 22, 2019 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

In the quest for new treatment options for depression, attention is being paid to the potential role of psychedelic drugs. Psilocybin is of particular interest given its mechanism of action, its benefits in early trials and its relatively low side effects burden. This viewpoint outlines a number of key issues that remain to be elucidated about its potential use in the clinical environment, including clarification of the profile of people most likely to benefit and those who might experience adverse effects, longer-term outcomes and the role of psychotherapeutic input alongside the drug itself. There are also opportunities to understand better, the neurobiology underpinning its effects.

Meikle, S. E., Liknaitzky, P., Rossell, S. L., Ross, M., Strauss, N., Thomas, N., … & Castle, D. J. (2019). Psilocybin-assisted therapy for depression: How do we advance the field?. Australian & New Zealand Journal of Psychiatry, 0004867419888575., https://doi.org/10.1177/0004867419888575
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The Impact of Ayahuasca on Suicidality: Results From a Randomized Controlled Trial.

November 19, 2019 / Ayahuasca, Depressive Disorders, Papers, Psychology, Publications / By / , , , , ,

Abstract

Suicide is a major public health problem. Given increasing suicide rates and limitations surrounding current interventions, there is an urgent need for innovative interventions for suicidality. Although ayahuasca has been shown to target mental health concerns associated with suicidality (i.e., depression and hopelessness), research has not yet explored the impact of ayahuasca on suicidality. Therefore, we conducted secondary analyses of a randomized placebo-controlled trial in which individuals with treatment-resistant depression were administered one dose of ayahuasca (n = 14) or placebo (n = 15). Suicidality was assessed by a trained psychiatrist at baseline, as well as 1 day, 2 days, and 7 days after the intervention. A fixed-effects linear mixed model, as well as between and within-groups Cohen’s d effect sizes were used to examine changes in suicidality. Controlling for baseline suicidality, we found a significant effect for time (p < .05). The effect of the intervention (i.e., ayahuasca vs. placebo) trended toward significance (p = .088). At all time points, we found medium between-group effect sizes (i.e., ayahuasca vs. placebo; day 1 Cohen’s d = 0.58; day 2 d = 0.56; day 7 d = 0.67), as well as large within-group (ayahuasca; day 1 Cohen’s d = 1.33; day 2 d = 1.42; day 7 d = 1.19) effect sizes, for decreases in suicidality. Conclusions: This research is the first to explore the impact of ayahuasca on suicidality. The findings suggest that ayahuasca may show potential as an intervention for suicidality. We highlight important limitations of the study, potential mechanisms, and future directions for research on ayahuasca as an intervention for suicidality. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02914769.

Zeifman, R., Palhano-Fontes, F., Hallak, J., Nunes, E. A., Maia-de-Oliveira, J. P., & de Araujo, D. B. (2019). The Impact of Ayahuasca on Suicidality: Results From a Randomized Controlled Trial. Frontiers in Pharmacology, 10, 1325.
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Distinct acute effects of LSD, MDMA, and D-amphetamine in healthy subjects.

November 16, 2019 / Anxiety Disorders / PTSD, LSD, MDMA, Papers, Psychology, Publications / By / , , , , ,

Abstract

Lysergic acid diethylamide (LSD) is a classic psychedelic, 3,4-methylenedioxymethamphetamine (MDMA) is an empathogen, and D-amphetamine is a classic stimulant. All three substances are used recreationally. LSD and MDMA are being investigated as medications to assist psychotherapy, and D-amphetamine is used for the treatment of attention-deficit/hyperactivity disorder. All three substances induce distinct acute subjective effects. However, differences in acute responses to these prototypical psychoactive substances have not been characterized in a controlled study. We investigated the acute autonomic, subjective, and endocrine effects of single doses of LSD (0.1 mg), MDMA (125 mg), D-amphetamine (40 mg), and placebo in a randomized, double-blind, cross-over study in 28 healthy subjects. All of the substances produced comparable increases in hemodynamic effects, body temperature, and pupil size, indicating equivalent autonomic responses at the doses used. LSD and MDMA increased heart rate more than D-amphetamine, and D-amphetamine increased blood pressure more than LSD and MDMA. LSD induced significantly higher ratings on the 5 Dimensions of Altered States of Consciousness scale and Mystical Experience Questionnaire than MDMA and D-amphetamine. LSD also produced greater subjective drug effects, ego dissolution, introversion, emotional excitation, anxiety, and inactivity than MDMA and D-amphetamine. LSD also induced greater impairments in subjective ratings of concentration, sense of time, and speed of thinking compared with MDMA and D-amphetamine. MDMA produced greater ratings of good drug effects, liking, high, and ego dissolution compared with D-amphetamine. D-Amphetamine increased ratings of activity and concentration compared with LSD. MDMA but not LSD or D-amphetamine increased plasma concentrations of oxytocin. None of the substances altered plasma concentrations of brain-derived neurotrophic factor. These results indicate clearly distinct acute effects of LSD, MDMA, and D-amphetamine and may assist the dose-finding in substance-assisted psychotherapy research.
Holze, F., Vizeli, P., Müller, F., Ley, L., Duerig, R., Varghese, N., … & Liechti, M. E. (2019). Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects. Neuropsychopharmacology, 1-11., https://doi.org/10.1038/s41386-019-0569-3
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Locomotor effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in mice: psychostimulant effects, stereotypy, and sensitization

November 15, 2019 / MDMA, Neuroscience, Papers, Pharmacology & Chemistry, Publications / By / , , ,

Abstract

Rationale

There is a renewed interest in the use of 3,4-methylenedioxymethamphetamine (MDMA) for treating psychiatric conditions. Although MDMA has entered phase II clinical trials and shows promise as an adjunct treatment, there is an extensive literature detailing the potential neurotoxicity and adverse neurobehavioral effects associated with MDMA use. Previous research indicates that the adverse effects of MDMA may be due to its metabolism into reactive catechols that can enter the brain and serve directly as neurotoxicants. One approach to mitigate MDMA’s potential for adverse effects is to reduce O-demethylation by deuterating the methylenedioxy ring of MDMA. There are no studies that have evaluated the effects of deuterating MDMA on behavioral outcomes.

Objectives

The purpose of the present study was to assess the motor-stimulant effects of deuterated MDMA (d2-MDMA) and compare them to MDMA in male mice.

Methods

Two experiments were performed to quantify mouse locomotor activity and to vary the drug administration regimen (single bolus administration or cumulative administration).

Results

The results of Experiments 1 and 2 indicate that d2-MDMA is less effective at eliciting horizontal locomotion than MDMA; however, the differences between the compounds diminish as the number of cumulative administrations increase. Both d2-MDMA and MDMA can elicit sensitized responses, and these effects cross-sensitize to the prototypical drug of abuse methamphetamine. Thus, d2-MDMA functions as a locomotor stimulant similar to MDMA, but, depending on the dosing regimen, may be less susceptible to inducing sensitization to stereotyped movements.

Conclusions

These findings indicate that d2-MDMA is behaviorally active and produces locomotor effects that are similar to MDMA, which warrant additional assessments of d2-MDMA’s behavioral and physiological effects to determine the conditions under which this compound may serve as a relatively safer alternative to MDMA for clinical use.
Berquist, M. D., Leth-Petersen, S., Kristensen, J. L., & Fantegrossi, W. E. (2020). Locomotor effects of 3, 4-methylenedioxymethamphetamine (MDMA) and its deuterated form in mice: psychostimulant effects, stereotypy, and sensitization. Psychopharmacology, 237(2), 431-442; https://doi.org/10.1007/s00213-019-05380-3

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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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