The probabilistic reversal learning task (PRL) is sometimes used in the context of major depressive disorder (MDD) to assess impairments in cognitive flexibility and feedback sensitivity because behavior in the task is sensitive to pharmacological interventions. Because traditional antidepressants are limited in their effectiveness, new drugs are needed to combat MDD. Ketamine has recently been...
Emerging evidence suggests that psychedelic experiences have the potential to change attitudes towards death and reduce death anxiety. Improved attitudes towards death, specifically reduced death anxiety, are of psychological significance for clinical and non-clinical populations alike. Despite this emerging evidence, little is known about the phenomenology of this potential outcome. To provide...
N, N-Dimethyltryptamine (DMT), a potent serotonergic psychedelic, bridges ancient wisdom and modern science. The mechanisms underlying its powerful psychedelic effects and out-of-body experiences continue to intrigue scientists. The functional role of DMT remains ambiguous. This paper explores the endogenous presence of DMT in the human body and its diverse neuroregulatory functions, which...
PsychopharmacologyApril 8, 2025Megan L Bertholomey, Camryn Forbes, Bryan D McElroy et al.3 citations
Alcohol use and major depressive disorder are frequently comorbid, with individuals diagnosed with a substance use disorder being nearly three times as likely to have major depression. Poor treatment responses are found for both disorders and are further complicated when they co-occur, underscoring the need for better therapies. One potential candidate is ketamine, which has been shown to have...
Little is known about motives of healthy volunteers to participate in psychedelic trials and how they appraise their study experience retrospectively. This paper explored reasons why healthy people register for psychedelic trials, factors that they considered to contribute to either positive or negative study experiences, and under which circumstances they would seek a psychedelic experience...
Since the earliest LSD research, psychedelics have been claimed to enhance autobiographical memory. Revisiting and processing autobiographical memories has further been suggested to be a major component of the therapeutic action of psychedelics. However, modern psychedelic research has largely neglected autobiographical elements of psychedelic experiences, and many vital questions remain...
RATIONALE: Despite the critical role of choice processes in substance use disorders, the neurobehavioral mechanisms guiding human decisions about drugs remain poorly understood. OBJECTIVES: We aimed to characterize the neural encoding of subjective value (SV) for cannabis versus non-drug rewards (snacks) in people who use cannabis on a near-daily/daily frequency (PWUCF) and assessed the impact...
With increasing legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis can impair cognition in young adults, it is critically important to understand how its consumption interacts with the cognitive profile of aged subjects, who are already at increased risk of decline. The current study was designed to determine how cannabis...
Previous studies have reported conflicting findings regarding the efficacy of esketamine in managing postoperative depression. While the positive effects of subanesthetic doses esketamine have been observed in treatment-resistant depression, the response to this medication in patients experiencing depression following surgery has not been consistent. Building upon the known impact of anesthesia...
Enhanced creativity is often cited as an effect of microdosing (taking repeated low doses of a psychedelic drug). There have been recent efforts to validate the reported effects of microdosing, however creativity remains a difficult construct to quantify. The current study aimed to assess microdosing's effects on creativity using a multimodal battery of tests as part of a randomised controlled...
Anecdotal reports suggest that psychedelic drugs can improve psychological wellbeing and social engagement in autistic people. However, there are few contemporary studies on this topic. To examine autistic participants' experiences with psychedelic drugs and the extent to which they attributed changes in mental health and social engagement to their most 'impactful' psychedelic experience. We...
PsychopharmacologyFebruary 1, 2025Maricela X. Martinez, Vanessa Alizo Vera, Christina M. Ruiz et al.1 citation
Adolescent cannabis use is linked to later-life changes in cognition, learning, and memory. Rodent experimental studies suggest Δ9-tetrahydrocannabinol (THC) influences development of circuits underlying these processes, especially in the prefrontal cortex, which matures during adolescence. We determined how 14 daily THC injections (5 mg/kg) during adolescence persistently impacts medial...
PsychopharmacologyJanuary 18, 2025Sharon R. Sznitman, Yoel A. Behar, Sheila Daniela Dicker-Oren et al.3 citations
Abstract Rationale To examine the acute effects of ayahuasca use and their relationship to sub-acute changes in affect and mindfulness in a non-clinical sample, addressing the need for a better understanding of ayahuasca’s immediate and short-term impacts as interest in its use grows. Objectives Using prospective ecological assessment, this study investigates how ayahuasca used at a 4-day...
Abstract Rationale Psychedelic-assisted therapy is increasingly applied within mental health treatment. Objectives This study focused on factors moderating changes in the acute and long-term effects of an individual psilocybin-assisted program on depression, anxiety, PTSD and personality structures by including demographic factors, subjective experience and degree of mystical type experiences...
There is increasing interest in establishing psychedelic research programs at academic medical centers. However, psychedelics are intensely psychoactive, carry considerable sociopolitical baggage, and most are Schedule I drugs, creating significant potential impediments to implementation. There is little formal guidance for investigators on navigating the complex on-the-ground obstacles...
PsychopharmacologyNovember 2024Huili Zhu, Longyu Wang, Xiaoxuan Wang et al.
The phenylalkylamine hallucinogen (-)-2,5-dimethoxy-4-methylamphetamine (DOM) exhibits an inverted U-shaped dose-response curve for both head twitch response (HTR) and locomotor activity in mice. Accumulated studies suggest that HTR and locomotor hyperactivity induced by DOM are mainly caused by the activation of serotonin 5-hydroxytryptamine 2 A receptor (5-HT2A receptor). However, the...
Recent reports have shown increased cannabis use among women, leading to growing concerns about cannabis use disorder (CUD). While there is preclinical evidence suggesting biological sex influences cannabinoid effects, human research remains scant. We investigated sex differences in the acute response to oral tetrahydrocannabinol (THC) in humans. 56 healthy men and women with prior exposure to...
Psychedelic-assisted psychotherapy (PAP) has emerged as a potential treatment for a variety of mental health conditions, including substance use disorders and depression. Current models of PAP emphasize the importance of psychotherapeutic support before, during, and after ingestion of a psychedelic to maximize safety and clinical benefit. Despite this ubiquitous assumption, there has been...
Treatments with the serotonergic psychedelic psilocybin are being investigated for multiple neuropsychiatric disorders. Because many patients with these disorders use selective serotonin reuptake inhibitors (SSRIs), understanding interactions between psilocybin and SSRIs is critical for evaluating the safety, efficacy, and scalability of psilocybin-based treatments. Current knowledge about...
Our study aimed to unravel the unknown mechanisms behind the exceptional efficacy of Psilocybin (PSI) in treating treatment-resistant depression (TRD). Focusing on Wistar-Kyoto (WKY) rats with a TRD phenotype and Wistar (WIS) rats as a normative comparison, we investigated behavioral and neuroplasticity-related responses to PSI, striving to shed light on the distinctive features of its...
PsychopharmacologyJuly 1, 2024Nathaniel A. Shanok, Sabrina Muzac, Leah Brown et al.7 citations
Major Depressive Disorder (MDD) is a pervasive psychiatric condition effecting approximately 21 million adults in the U.S. (8.4%). An estimated 30-60% of patients are resistant to traditional treatment approaches (medications and talk-therapy), alluding to the need for additional options. Two promising treatment modalities include transcranial magnetic stimulation (TMS) and ketamine infusions;...
Ibogaine is a potent atypical psychedelic that has gained considerable attention due to its antiaddictive and antidepressant properties in preclinical and clinical studies. Previous research from our group showed that ibogaine suppresses sleep and produces an altered wakefulness state, which resembles natural REM sleep. However, after systemic administration, ibogaine is rapidly metabolized to...
Ketamine produces dissociative, psychomimetic, anxiolytic, antidepressant, and anesthetic effects in a dose dependent manner. It has a complex mechanism of action that involve alterations in other glutamate receptors. The metabotropic glutamate receptor 5 (mGluR5) has been investigated in relation to the psychotic and anesthetic properties of ketamine, while its role in mediating the...
Recent years have seen a resurgence in randomized, placebo controlled trials (RCTs) utilizing non-classical psychedelics (e.g. 3,4-methyl enedioxy methamphetamine [MDMA]), and classical psychedelics (e.g. psilocybin, lysergic acid diethylamide [LSD], and N,N-dimethyltryptamine [DMT/ayahuasca]) in conjunction with assisted therapy (AT) for psychiatric disorders. A notable methodological...
Recent research with classic psychedelics suggests significant therapeutic potential, particularly for neuropsychiatric disorders. A mediating influence behind symptom resolution is thought to be the personal insight - at times, bordering on the mystical - one acquires during the acute phase of a psychedelic session. Indeed, current clinical trials have found strong correlations between the...