On Minimizing Risk and Harm in the Use of Psychedelics.

Objective: This article outlines recommendations from 30 psychedelic researchers on how to create a better psychedelic safety net.

Methods: A survey of 30 psychedelic researchers asked them to identify key critical research gaps around psychedelic harm and safety.

Results: The critical research gaps identified by the authors included defining the main types of psychedelic harm, the predictors of those harms, and the most effective way to treat those harms.

Learning how to make use of dissociative therapies.

Dissociative therapies are being increasingly explored for their psychiatric applications, although questions remain about how they work and how best to use them. In exploring these questions, this review highlights six key areas of clinical relevance: (1) The possible contributions of functional unblinding when interpreting efficacy data; (2) The degree to which the therapeutic effects of dissociative therapies can be distinguished from the transient forms of relief seen with recreational drug use; (3) Understanding the construct of dissociation as it is tasked with describing the function of dissociative drugs; (4) The investigation of subjective drug effects as predictors of therapeutic outcome; (5) Similarities and differences in the effects of dissociative and classic psychedelics; and (6) The anticipated need for judicious prescribing/deprescribing resources as dissociative therapies proliferate.

Shame, Guilt and Psychedelic Experience: Results from a Prospective, Longitudinal Survey of Real-World Psilocybin Use.

The classic psychedelic psilocybin has attracted special interest across clinical and non-clinical settings as a potential tool for mental health. Despite increasing attention to challenging psychedelic experiences, few studies have explored the relevance of shame-related processes with psychedelic use. This prospective, longitudinal study involved sequential, automated, web-based surveys that collected data from 679 adults planning to use psilocybin in naturalistic settings at timepoints before and after psilocybin use.

At-home, telehealth-supported ketamine treatment for depression: Findings from longitudinal, machine learning and symptom network analysis of real-world data.

Background: Improving safe and effective access to ketamine therapy is of high priority given the growing burden of mental illness. Telehealth-supported administration of sublingual ketamine is being explored toward this goal.

Methods: In this longitudinal study, moderately-to-severely depressed patients received four doses of ketamine at home over four weeks within a supportive digital health context.

Double-Blind Comparison of the Two Hallucinogens Dextromethorphan and Psilocybin: Experience-Dependent and Enduring Psychological Effects in Healthy Volunteers.

Rationale: N-methyl-D-aspartate receptor-mediated dissociatives and serotonergic hallucinogens are being increasingly used in therapeutic interventions that involve nonordinary states of consciousness and may represent a unique mental health paradigm wherein pharmacologically induced experiences are conducive to psychological well-being.

Objective: The aim of this study was to further understand how the phenomenological and health-promoting effects of high-dose dextromethorphan (DXM) compared to psilocybin in the same participants when administered under experimental conditions that are typical of therapeutic psychedelic trials.

Methods: Single, acute oral doses of DXM (400 mg/70 kg), psilocybin (10, 20, 30 mg/70 kg), and inactive placebo were administered under double-blind and psychologically supportive conditions to 20 healthy participants with histories of hallucinogen use.

Naturalistic psilocybin use is associated with persisting improvements in mental health and wellbeing: results from a prospective, longitudinal survey.

Introduction: The classic psychedelic psilocybin, found in some mushroom species, has received renewed interest in clinical research, showing potential mental health benefits in preliminary trials. Naturalistic use of psilocybin outside of research settings has increased in recent years, though data on the public health impact of such use remain limited.

Methods: This prospective, longitudinal study comprised six sequential automated web-based surveys that collected data from adults planning to take psilocybin outside clinical research: at time of consent, 2 weeks before, the day before, 1-3 days after, 2-4 weeks after, and 2-3 months after psilocybin use.

Reconsidering "dissociation" as a predictor of antidepressant efficacy for esketamine.

Rationale: The relationship between subjective drug experience and antidepressant outcomes for ketamine derivatives is poorly understood but of high clinical relevance. Esketamine is the patented (S)-enantiomer of ketamine and has regulatory approval for psychiatric applications.

Objectives: We examined the relationship between acute dissociation, as measured by the Clinician-Administered Dissociative States Scale (CADSS), and antidepressant efficacy, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), for esketamine across the 4-week induction phase of treatment.

Mapping consent practices for outpatient psychiatric use of ketamine.

Background: Given increasing community-based and off-label use of ketamine for psychiatric indications, we examined current informed consent processes from a convenience sample of outpatient ketamine clinics to identify areas of congruence with current evidence and opportunities for growth.

Methods: Using a rubric developed from existing practice guidelines, we conducted an exploratory analysis of informed consent documents (IC-Docs) from 23 American clinics offering ketamine as a psychiatric treatment. Domains assessed included clinical content, procedures, and syntax.

Toward Synergies of Ketamine and Psychotherapy.

Ketamine is a dissociative drug that has been used medically since the 1970s primarily as an anesthetic agent but also for various psychiatric applications. Anecdotal reports and clinical research suggest substantial potential for ketamine as a treatment in conjunction with psychological interventions. Here, we review historical and modern approaches to the use of ketamine with psychotherapy, discuss the clinical relevance of ketamine's acute psychoactive effects, propose a unique model for using esketamine (one isomeric form of ketamine) with Acceptance and Commitment Therapy (ACT), and suggest considerations for moving medication-assisted psychotherapy forward as a field.

Deep transcranial magnetic stimulation for obsessive compulsive disorder.

Introduction: Obsessive-compulsive disorder (OCD) is a common psychiatric disorder that can be chronic and debilitating if not properly treated. Current first-line treatments for OCD include cognitive-behavioral therapy with exposure and response prevention and serotonin uptake inhibitor medications; however, these therapies are not effective for all individuals.

Areas Covered: Deep transcranial magnetic stimulation (dTMS) has been hypothesized to be an effective alternative for individuals with treatment-resistant OCD.

The relationship between subjective effects induced by a single dose of ketamine and treatment response in patients with major depressive disorder: A systematic review.

Objective: The relationship between ketamine's hallucinogenic- and dissociative-type effects and antidepressant mechanism of action is poorly understood. This paper reviewed the correlation between subjective effects defined by various psychometric scales and observed clinical outcomes in the treatment of patients with Major Depressive Disorder (MDD).

Methods: Based on PRISMA guidelines, we reviewed the dissociative and psychotomimetic mental state induced with ketamine during MDD treatment.

Recovery from impaired working memory performance during chronic Δ-9-tetrahydrocannabinol administration to adolescent rhesus monkeys.

Background: The relationship between adolescent cannabis use and susceptibility to persistent cognitive impairments is poorly understood.

Aims: We examined the effects of repeated exposure to Δ-9-tetrahydrocannabinol (THC) on reinforcement-related learning and performance of spatial working memory (WM) tasks of varying difficulty in adolescent monkeys.

Methods: Seven pairs of male adolescent rhesus monkeys, matched for baseline cognitive performance, received vehicle or THC intravenously 5 days/week for 12 months.

Guanfacine Attenuates Adverse Effects of Dronabinol (THC) on Working Memory in Adolescent-Onset Heavy Cannabis Users: A Pilot Study.

The cannabinoid-1 receptor (CB1R) agonist Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, adversely effects working memory performance in humans. The α2A-adrenoceptor (AR) agonist guanfacine improves working memory performance in humans. The authors aimed to determine the effects of short-term (6 days) treatment with guanfacine on adverse cognitive effects produced by THC.

"Just one bad high:" considering synthetic cannabinoid outcome expectancies in adolescents.

Background/objectives: Certain medical consequences seem unique to synthetic cannabinoid (SC) and not cannabis use. We report the case of an adolescent, whose drug expectancies appear to minimize the severity of SC-related adverse events.

Methods/results: An 18-year-old male presented with altered mental status and seizure, complicated by respiratory failure.