Background/aims: Given high rates of depression and suicide among marginalized women, and increasing calls to integrate trauma-informed biomedical and community-led structural interventions, this study longitudinally examines the potential moderating effect of psychedelic use on the relationship between other illicit drug use and suicide risk. Methods: Data (2010–2017) were drawn from a...
Oxidative stress and mitochondrial dysfunction have been implicated in the pathophysiology of schizophrenia. We investigated whether antipsychotic clozapine modulates nicotinamide adenine dinucleotide phosphate oxidase and mitochondrial burdens induced by phencyclidine in mice. We examined the effect of clozapine on nicotinamide adenine dinucleotide phosphate oxidase activation, mitochondrial...
Intravenous ketamine has been established as an efficacious and safe treatment, with transient effect, for treatment-resistant depression. However, the effectiveness of intravenous ketamine in non-research settings and with ultraresistant depression patients remains understudied. This study aims to measure the response and remission rates in ultraresistant depression patients in a clinical...
Ketamine has been shown to produce a rapid and potent antidepressant response in patients with treatment-resistant depression. Currently ketamine is most commonly administered as a 40-minute intravenous infusion, though it is unknown whether this is the optimal route of administration. To determine the plasma concentration time course of the R- and S-enantiomers of ketamine and norketamine...
BACKGROUND: Ketamine has proven to have rapid, robust antidepressant effects on treatment-resistant depression. However, whether repeated ketamine infusions would cause short-and long-term neurocognitive impairments was not clear. Our aims were to investigate the neurocognitive effects of six ketamine infusions and to examine the association between these infusions and the antidepressant...
BACKGROUND: Previously, the authors have developed a model of how reward-seeking and distress- avoiding behaviour is regulated by the human brain. The forebrain's evolution in vertebrates was taken as a starting point. AIMS: The authors want to inspire colleagues to study in particular the pharmacological effects on the described ancient forebrain structures in order to modify specific symptoms...
Background: Lysergic acid diethylamide (LSD) and psilocybin are serotonergic hallucinogens that are used primarily for recreational abuse. Small studies evaluated the efficacy of LSD and psilocybin for several psychiatric conditions. There are limited safety or toxicity data for either of these substances, especially in large populations. Methods: This was a retrospective analysis of...
5-Methoxy- N,N-dimethyltryptamine (5-MeO-DMT) is a psychoactive compound found in several plants and in high concentrations in Bufo alvarius toad venom. Synthetic, toad, and plant-sourced 5-MeO-DMT are used for spiritual and recreational purposes and may have psychotherapeutic effects. However, the use of 5-MeO-DMT is not well understood. Therefore, we examined patterns of use, motivations for...
Recent research on psychedelics and hypnosis demonstrates the value of both methods in the treatment of a range of psychopathologies with overlapping applications and neurophenomenological features. The potential of harnessing the power of suggestion to influence the phenomenological response to psychedelics toward more therapeutic action has remained unexplored in recent research and thereby...
Aim: The aim of the current study was to investigate the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects. Methods: Healthy participants ( n=12) were given three escalating doses of oral psilocybin (0.3 mg/kg; 0.45 mg/kg; 0.6 mg/kg) or (18.8–36.6 mg; 27.1–54.0 mg; 36.3–59.2 mg) a minimum of four weeks apart in a...
Background: Recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilitated addiction treatment interventions. Fifteen participants completed a psilocybin-facilitated smoking cessation pilot study between 2009 and 2015. Aims: The aims of this study were as follows: (1) to identify perceived mechanisms of change leading to smoking cessation in the pilot study; (2) to...
BACKGROUND: Substituted piperazines comprise a substantial proportion of the novel psychoactive substance market. Among the most widely abused piperazine compounds are meta-chlorophenylpiperazine (mCPP), tri-fluoromethylphenylpiperazine (TFMPP), and, especially, benzylpiperazine (BZP), which are commonly incorporated, either alone or in combination, in illicit "party pills" or "ecstasy"...
In this maintenance treatment study, we sought to evaluate the effect on anxiety ratings, safety and tolerability of 3 months of weekly ketamine in 20 patients with treatment-refractory DSM IV generalised anxiety disorder (GAD) and/or social anxiety disorder (SAD), and subsequent assessment of remission post-treatment. This was an uncontrolled open-label study in 20 patients who had been...
Background: Recent evidence suggests that psychedelic use predicts reduced perpetration of intimate partner violence among men involved in the criminal justice system. However, the extent to which this association generalizes to community samples has not been examined, and potential mechanisms underlying this association have not been directly explored. Aims: The present study examined the...
BACKGROUND: Neuroimaging studies imply that the regular use of ±3,4-methylenedioxymethamphetamine (MDMA), the major constituent of ecstasy pills, alters the brain's serotonergic system in a dose-dependent manner. However, the relevance of these findings remains unclear due to limited knowledge about the ecstasy/MDMA use pattern of real-life users. AIMS: We examined the representativeness of...
Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments. This randomised, double-blind, placebo-controlled pilot study compared a 4-week course...
Lagging behind rapid changes to state laws, societal views, and medical practice is the scientific investigation of cannabis's impact on the human brain. While several brain imaging studies have contributed important insight into neurobiological alterations linked with cannabis use, our understanding remains limited. Here, we sought to delineate those brain regions that consistently demonstrate...
Cannabis use disorders are frequently comorbid in patients with a psychotic disorder and are associated with worse outcomes. To date there are no proven effective strategies to achieve cannabis abstinence in this population. An alternative for abstinence might be harm reduction, i.e. replacing the use of street cannabis with high tetrahydrocannabinol and low cannabidiol levels by medicinal...
Psychedelic drugs are making waves as modern trials support their therapeutic potential and various media continue to pique public interest. In this opinion piece, we draw attention to a long-recognised component of the psychedelic treatment model, namely ‘set’ and ‘setting’ – subsumed here under the umbrella term ‘context’. We highlight: (a) the pharmacological mechanisms of classic...
Major depressive disorder is a leading cause of disability globally. Improvements in the efficacy of antidepressant therapy are needed as a high proportion (>40%) of individuals with major depressive disorder fail to respond adequately to current treatments. The non-selective N-methyl-D-aspartate receptor channel blocker, (±)-ketamine, has been reported to produce a rapid and long-lasting...
Rationale: Previous research suggests that classical psychedelic compounds can induce lasting changes in personality traits, attitudes and beliefs in both healthy subjects and patient populations. Aim: Here we sought to investigate the effects of psilocybin on nature relatedness and libertarian–authoritarian political perspective in patients with treatment-resistant depression (TRD). Methods:...
The pineal gland has a romantic history, from pharaonic Egypt, where it was equated with the eye of Horus, through various religious traditions, where it was considered the seat of the soul, the third eye, etc. Recent incarnations of these notions have suggested that N,N-dimethyltryptamine is secreted by the pineal gland at birth, during dreaming, and at near death to produce out of body...
Criminal behavior exacts a large toll on society and is resistant to intervention. Some evidence suggests classic psychedelics may inhibit criminal behavior, but the extent of these effects has not been comprehensively explored. In this study, we tested the relationships of classic psychedelic use and psilocybin use per se with criminal behavior among over 480,000 United States adult...
BACKGROUND: This study sought to reproduce, in a larger sample, previous findings of a correlation between smaller raw 3-Tesla (3T) hippocampal volumes and improved antidepressant efficacy of ketamine in individuals with major depressive disorder (MDD). A secondary analysis stratified subjects according to functional BDNF rs6265 (val66met) genotype. METHODS: Unmedicated subjects with...
Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2)...