Developing an Ethics and Policy Framework for Psychedelic Clinical Care: A Consensus Statement.

Importance: As government agencies around the globe contemplate approval of the first psychedelic medicines, many questions remain about their ethical integration into mainstream medical practice.

Objective: To identify key ethics and policy issues related to the eventual integration of psychedelic therapies into clinical practice.

Evidence Review: From June 9 to 12, 2023, 27 individuals representing the perspectives of clinicians, researchers, Indigenous groups, industry, philanthropy, veterans, retreat facilitators, training programs, and bioethicists convened at the Banbury Center at Cold Spring Harbor Laboratory.

Novel Benzofuran Derivatives Induce Monoamine Release and Substitute for the Discriminative Stimulus Effects of 3,4-Methylenedioxymethamphetamine.

3,4-Methylenedioxymethamphetamine (MDMA) has shown efficacy as a medication adjunct for treating post-traumatic stress disorder (PTSD). However, MDMA is also used in nonmedical contexts that pose risk for cardiovascular and neurologic complications. It is well established that MDMA exerts its effects by stimulating transporter-mediated release of the monoamines 5-hydroxytryptamine (5-HT), norepinephrine, and dopamine.

Detection of acute 3,4-methylenedioxymethamphetamine (MDMA) effects across protocols using automated natural language processing.

The detection of changes in mental states such as those caused by psychoactive drugs relies on clinical assessments that are inherently subjective. Automated speech analysis may represent a novel method to detect objective markers, which could help improve the characterization of these mental states. In this study, we employed computer-extracted speech features from multiple domains (acoustic, semantic, and psycholinguistic) to assess mental states after controlled administration of 3,4-methylenedioxymethamphetamine (MDMA) and intranasal oxytocin.

Effects of the Psychedelic Amphetamine MDA (3,4-Methylenedioxyamphetamine) in Healthy Volunteers.

Entactogens such as 3,4-Methylenedioxymethamphetamine (MDMA, "molly", "ecstasy") appear to have unusual, potentially therapeutic, emotional effects. Understanding their mechanisms can benefit from clinical experiments with related drugs. Yet the first known drug with such properties, 3,4-Methylenedioxyamphetamine (MDA), remains poorly studied and its pharmacokinetics in humans are unknown.

The effects of MDMA on socio-emotional processing: Does MDMA differ from other stimulants?

±3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that enhances sociability and feelings of closeness with others. These "prosocial" effects appear to motivate the recreational use of MDMA and may also form the basis of its potential as an adjunct to psychotherapy. However, the extent to which MDMA differs from prototypic stimulant drugs, such as dextroamphetamine, methamphetamine, and methylphenidate, in either its behavioral effects or mechanisms of action, is not fully known.

MDMA Impairs Response to Water Intake in Healthy Volunteers.

Hyponatremia is a serious complication of 3,4-methylenedioxymethamphetamine (MDMA) use. We investigated potential mechanisms in two double-blind, placebo-controlled studies. In Study 1, healthy drug-experienced volunteers received MDMA or placebo alone and in combination with the alpha-1 adrenergic inverse agonist prazosin, used as a positive control to release antidiuretic hormone (ADH).

Effects of 3,4-methylenedioxymethamphetamine on socioemotional feelings, authenticity, and autobiographical disclosure in healthy volunteers in a controlled setting.

The drug 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy", "molly") is a widely used illicit drug and experimental adjunct to psychotherapy. MDMA has unusual, poorly understood socioemotional effects, including feelings of interpersonal closeness and sociability. To better understand these effects, we conducted a small (n=12) within-subjects double-blind placebo controlled study of the effects of 1.

Intimate insight: MDMA changes how people talk about significant others.

Rationale: ±3,4-methylenedioxymethamphetamine (MDMA) is widely believed to increase sociability. The drug alters speech production and fluency, and may influence speech content. Here, we investigated the effect of MDMA on speech content, which may reveal how this drug affects social interactions.

MDMA effects consistent across laboratories.

Rationale: Several laboratories have conducted placebo-controlled drug challenge studies with 3,4-methylenedioxymethamphetamine (MDMA), providing a unique source of data to examine the reliability of the acute effects of the drug across subject samples and settings. We examined the subjective and physiological responses to the drug across three different laboratories and investigated the influence of prior MDMA use.

Methods: Overall, 220 healthy volunteers with varying levels of previous MDMA experience participated in laboratory-based studies in which they received placebo or MDMA orally (1.

Test-retest reliability of behavioral measures of impulsive choice, impulsive action, and inattention.

Behavioral measures of impulsivity are widely used in substance abuse research, yet relatively little attention has been devoted to establishing their psychometric properties, especially their reliability over repeated administration. The current study examined the test-retest reliability of a battery of standardized behavioral impulsivity tasks, including measures of impulsive choice (i.e.

Psychopharmacology of theobromine in healthy volunteers.

Background: Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited.

Objectives: We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants.

Developing biomarkers for methamphetamine addiction.

There are an estimated 11.7 million methamphetamine (MA) abusers in the United States and epidemics of MA addiction are occurring worldwide. In our human laboratory and outpatient clinical trials we use innovative methods to quantify the severity of MA addiction and test biomarkers that may predict response to therapy or risk of relapse.

A method to quantify illicit intake of drugs from urine: methamphetamine.

Qualitative urinalysis can verify abstinence of drug misuse but cannot detect changes in drug intake. For drugs with slow elimination, such as methamphetamine (MA), a single episode of abuse can result in up to 5 days of positive urine drug screens. Thus, interventions that produce substantial decreases in drug use but do not achieve almost complete abstinence are classified as ineffective.

Investigating the mechanisms of hallucinogen-induced visions using 3,4-methylenedioxyamphetamine (MDA): a randomized controlled trial in humans.

Background: The mechanisms of drug-induced visions are poorly understood. Very few serotonergic hallucinogens have been studied in humans in decades, despite widespread use of these drugs and potential relevance of their mechanisms to hallucinations occurring in psychiatric and neurological disorders.

Methodology/principal Findings: We investigated the mechanisms of hallucinogen-induced visions by measuring the visual and perceptual effects of the hallucinogenic serotonin 5-HT2AR receptor agonist and monoamine releaser, 3,4-methylenedioxyamphetamine (MDA), in a double-blind placebo-controlled study.

Lack of effect of sublingual salvinorin A, a naturally occurring kappa opioid, in humans: a placebo-controlled trial.

Rationale: Salvinorin A (SA) is a highly selective kappa opioid receptor agonist and the putative psychoactive compound in Salvia divinorum (SD), an increasingly abused hallucinogenic plant.

Objectives: The objectives of this study were to characterize the physiological and subjective effects of SA versus placebo and measure drug and metabolite levels.

Methods: Sublingual SA doses up to 4 mg were administered in dimethyl sulfoxide/polyethylene glycol 400 solution to eight SD-experienced subjects using a placebo-controlled ascending-dose design.

An examination of drug craving over time in abstinent methamphetamine users.

Craving for addictive drugs may predict relapse in abstinent addicts. To assess relationships between craving and use, we examined changes in craving for methamphetamine (MA) in a sample of 865 outpatients in a multisite 16-week MA-treatment study. Craving was assessed on a 0-100 scale, and MA use was assessed by self-report and confirmed by urinalysis.

Use patterns and self-reported effects of Salvia divinorum: an internet-based survey.

Background: There is growing use of Salvia divinorum (SD), a psychoactive plant that produces hallucinogen-like effects through a kappa opioid receptor (KOR) mechanism. Little is known about KOR agonist effects in humans and about users of SD.

Objectives: To characterize the reasons, methods, and reported consequences of SD use.

Estimating the intake of abused methamphetamines using experimenter-administered deuterium labeled R-methamphetamine: selection of the R-methamphetamine dose.

All addictive drugs produce tolerance and addicts compensate by increasing drug exposure. Thus, the quantity of illicit drug ingested is related to the severity of addiction. Unfortunately, there are no objective methods to estimate intake for most addictive drugs.

Imagery scripts and a computerized subtraction stress task both induce stress in methamphetamine users: a controlled laboratory study.

Patients treated for methamphetamine (MA) dependence have a high rate of relapse, and stress is thought to play a key role. We sought to develop a computerized procedure for experimentally inducing stress in MA users. In a within-subjects design, we compared a computerized subtraction stress task (SST) to personalized stress-imagery scripts and a control condition (neutral imagery) in 9 former MA users, recruited in San Francisco in 2006-2007.

Role of endocannabinoids in 5-HT2 receptor-mediated effects.

Endocannabinoids are lipid retrograde messengers that can be released by postsynaptic depolarization and/or activation of certain metabotropic receptors. We review a recent report that activation of metabotropic 5-HT2 receptors by endogenous serotonin induces the release of endocannabinoids in the olivary nucleus and suppresses glutamatergic input through a presynaptic action. This serotonin-endocannabinoid interaction has implications in the pathophysiology of pain and mental illness and raises the possibility that drugs targeting the 5-HT2 receptor may act by modulating endocannabinoid release.

Preventing problems in Ecstasy users: reduce use to reduce harm.

Increasing use of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") has been accompanied by concern about acute and possible long-term toxicity. This article discusses acute serious toxicity, chronic toxicity, and common problems associated with Ecstasy use, as well as the implications of these areas for prevention programs targeted at current Ecstasy users. The low incidence of serious adverse events in users creates difficulties for attempts to develop harm reduction recommendations.

Subjective and hormonal effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans.

Rationale: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely used phenethylamine. Reports have described the effects of MDMA in a controlled laboratory setting, but the full range of effects of MDMA in humans is still not completely characterized.

Objectives: To describe the physiological, subjective, and hormonal changes after single doses of MDMA in a laboratory setting and examine relationships between these effects.