Music as an Intervention to Improve the Hemodynamic Response of Ketamine in Depression: A Randomized Clinical Trial.

This randomized clinical trial explores whether music improves the hemodynamic response of ketamine among patients with treatment-resistant depression in Canada.

Ayahuasca in the treatment of posttraumatic stress disorder: Mixed-methods case series evaluation in military combat veterans.

OBJECTIVE: Although ayahuasca-a plant-based psychedelic-is discussed as promising in the treatment of posttraumatic stress disorder (PTSD), evidence so far remains limited to retrospective case reports and qualitative surveys. No study to date has examined whether ayahuasca results in prospective and clinically meaningful changes in trauma symptoms across individuals with PTSD symptoms. METHOD: To address this gap, we conducted a convergent mixed-methods case series study on eight military veterans with PTSD who participated in a 3-day ayahuasca intervention in Central America. Clinically meaningful changes from pre- to posttreatment and at a 3-month follow-up were assessed in three ways using: (a) PTSD checklist-5 (PCL-5); (b) experience sampling measurement of momentary PTSD and mood symptoms; and (c) an open-ended survey on perceived benefits. RESULTS: The majority (87.5%; 7/8) of participants demonstrated reliable and/or clinically significant changes in PCL-5 symptoms by posttreatment, which were maintained by 70% (5/7) of veterans by the 3-month follow-up. On average, veterans also reported significant improvements in momentary PTSD symptoms, as well as negative and positive affect in daily life posttreatment, with 63% (5/8) reporting moderate-to-large improvements in these domains. Broad themes characterizing the perceived benefits of ayahuasca included deep positive emotions, decentering/acceptance, and purpose in life; adverse acute experiences were, however, reported. CONCLUSIONS: This study provides preliminary support for the clinically meaningful and lasting benefits of a brief ayahuasca intervention on PTSD/mood symptoms in military veterans. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Intravenous ketamine for benzodiazepine deprescription and withdrawal management in treatment-resistant depression: a preliminary report.

We present the first evidence that sub-anesthetic ketamine infusions for treatment resistant depression (TRD) may facilitate deprescription of long-term benzodiazepine/z-drugs (BZDRs). Long-term BZDR prescriptions are potentially harmful yet common, partly because of challenging withdrawal symptoms. Few pharmacological interventions have evidence for facilitating BZDR discontinuation, and none in patients actively suffering from TRD. In this ambi-directional cohort study, discontinuation of long-term (>6 month) BZDRs was attempted in 22 patients with severe unipolar or bipolar TRD receiving a course of six subanesthetic ketamine infusions over four weeks. We investigated the rates of successful BZDRs deprescription, trajectories of acute psychological withdrawal symptoms, and subsequent BZDRs abstinence during a mean follow-up of 1 year (primary outcome). Clinically significant deteriorations in depression, anxiety, sleep, and/or suicidality during the acute BZDR discontinuation phase were measured by repeated standardized scales and analyzed by latent growth curve models and percent correct classification analysis. Of the 22 eligible patients, all enrolled in this study and 91% (20/22) successfully discontinued all BZDRs by the end of the 4-week intervention, confirmed by urinary analyses. Less than 25% of discontinuers experienced any significant worsening of anxiety, depression, sleep difficulties, or suicidality during treatment. During follow-up (mean [range] duration, 12 [3-24] months), 64% (14/22) of patients remained abstinent from any BZDRs. These preliminary results suggest that ketamine infusions for TRD may facilitate the deprescription of BZDRs, even in patients with active depressive symptoms and significant comorbidity. Further investigation is warranted into this potential novel application of ketamine.

Microdosing psychedelics: Demographics, practices, and psychiatric comorbidities.

RATIONALE: Microdosing psychedelics - the practice of consuming small, sub-hallucinogenic doses of substances such as LSD or psilocybin - is gaining attention in popular media but remains poorly characterized. Contemporary studies of psychedelic microdosing have yet to report the basic psychiatric descriptors of psychedelic microdosers. OBJECTIVES: To examine the practices and demographics of a population of psychedelic microdosers - including their psychiatric diagnoses, prescription medications, and recreational substance use patterns - to develop a foundation on which to conduct future clinical research. METHODS: Participants (n = 909; Mage = 26.9, SD = 8.6; male = 83.2%; White/European = 79.1%) recruited primarily from the online forum Reddit completed an anonymous online survey. Respondents who reported using LSD, psilocybin, or both for microdosing were grouped and compared with non-microdosing respondents using exploratory odds ratio testing on demographic variables, rates of psychiatric diagnoses, and past-year recreational substance use. RESULTS: Of microdosers, most reported using LSD (59.3%; Mdose = 13 mcg, or 11.3% of one tab) or psilocybin (25.9%; Mdose = 0.3 g of dried psilocybin mushrooms) on a one-day-on, two-days-off schedule. Compared with non-microdosers, microdosers were significantly less likely to report a history of substance use disorders (SUDs; OR = 0.17 (95% CI: 0.05-0.56)) or anxiety disorders (OR = 0.61 (95% CI: 0.41-0.91)). Microdosers were also more likely to report recent recreational substance use compared with non-microdosers (OR = 5.2 (95% CI: 2.7-10.8)). CONCLUSIONS: Well-designed randomized controlled trials are needed to evaluate the safety and tolerability of this practice in clinical populations and to test claims about potential benefits.

Psychedelic microdosing benefits and challenges: an empirical codebook.

BACKGROUND: Microdosing psychedelics is the practice of consuming very low, sub-hallucinogenic doses of a psychedelic substance, such as lysergic acid diethylamide (LSD) or psilocybin-containing mushrooms. According to media reports, microdosing has grown in popularity, yet the scientific literature contains minimal research on this practice. There has been limited reporting on adverse events associated with microdosing, and the experiences of microdosers in community samples have not been categorized. METHODS: In the present study, we develop a codebook of microdosing benefits and challenges (MDBC) based on the qualitative reports of a real-world sample of 278 microdosers. RESULTS: We describe novel findings, both in terms of beneficial outcomes, such as improved mood (26.6%) and focus (14.8%), and in terms of challenging outcomes, such as physiological discomfort (18.0%) and increased anxiety (6.7%). We also show parallels between benefits and drawbacks and discuss the implications of these results. We probe for substance-dependent differences, finding that psilocybin-only users report the benefits of microdosing were more important than other users report. CONCLUSIONS: These mixed-methods results help summarize and frame the experiences reported by an active microdosing community as high-potential avenues for future scientific research. The MDBC taxonomy reported here informs future research, leveraging participant reports to distil the highest-potential intervention targets so research funding can be efficiently allocated. Microdosing research complements the full-dose literature as clinical treatments are developed and neuropharmacological mechanisms are sought. This framework aims to inform researchers and clinicians as experimental microdosing research begins in earnest in the years to come.

Microdosing psychedelics: personality, mental health, and creativity differences in microdosers.

RATIONALE: Microdosing psychedelics-the regular consumption of small amounts of psychedelic substances such as LSD or psilocybin-is a growing trend in popular culture. Recent studies on full-dose psychedelic psychotherapy reveal promising benefits for mental well-being, especially for depression and end-of-life anxiety. While full-dose therapies include perception-distorting properties, microdosing mayprovide complementary clinical benefits using lower-risk, non-hallucinogenic doses. OBJECTIVES: This pre-registered study aimed to investigate whether microdosing psychedelics is related to differences in personality, mental health, and creativity. METHODS: In this observational study, respondents recruited from online forums self-reported their microdosing behaviors and completed questionnaires concerning dysfunctional attitudes, wisdom, negative emotionality, open-mindedness, and mood. Respondents also performed the Unusual Uses Task to assess their creativity. RESULTS: Current and former microdosers scored lower on measures of dysfunctional attitudes (p < 0.001, r = - 0.92) and negative emotionality (p = 0.009, r = - 0.85) and higher on wisdom (p < 0.001, r = 0.88), openmindedness(p = 0.027, r = 0.67), and creativity (p < 0.001, r = 0.15) when compared to non-microdosing controls. CONCLUSIONS: These findings provide promising initial evidence that warrants controlled experimental research to directly test safety and clinical efficacy. As microdoses are easier to administer than full-doses, this new paradigm has the exciting potential to shape future psychedelic research.