OBJECTIVES: People with bipolar disorder (BD) spend more time depressed than manic/hypomanic, and depression is associated with greater impairments in psychosocial functioning and quality of life than mania/hypomania. Emerging evidence suggests psilocybin, the psychoactive compound in "magic mushrooms," is a promising treatment for unipolar depression. Clini...
Several lines of evidence suggest that classic hallucinogens such as psilocybin can facilitate behavior change in addictions such as alcohol dependence. The proposed investigation is a multi-site, double-blind active-controlled trial (n = 180, 90 per group) contrasting the acute and persisting effects of psilocybin to those of diphenhydramine in the context ...
Patients characterized by stress-related disorders such as depression display elevated circulating concentrations of pro-inflammatory cytokines and a hyperactive HPA axis. Psychedelics are demonstrating promising results in treatment of such disorders, however the mechanisms of their therapeutic effects are still unknown. To date the evidence of acute and pe...
Microdosing-the intermittent ingestion of minute, sub-hallucinogenic amounts of psychedelic substances, repeatedly and over time-has become a widespread, albeit largely understudied, phenomenon. Regulations around using psychedelics at any dose-micro, mini, macro, or mega-pose all sorts of difficulties for those who wish to systematically study the effects o...
Psychedelic substances have played important roles in diverse cultures, and ingesting various plant preparations to evoke altered states of consciousness has been described throughout recorded history. Accounts of the subjective effects of psychedelics typically focus on spiritual and mystical-type experiences, including feelings of unity, sacredness, and tr...
BackgroundPreliminary results from randomized controlled studies as well as identified molecular, cellular, and circuit targets of select psychedelics (e.g., psilocybin) suggest that their effects are transdiagnostic. In this review, we exploit the Research Domain Criteria (RDoC) transdiagnostic framework, to synthesize extant literature on psilocybin.Object...
Psychiatric illnesses - such as major depressive disorder, anxiety disorder, substance use disorder, and posttraumatic stress disorder (PTSD) - are widely prevalent and represent a substantial health burden worldwide. Yet, conventional medications for mental illnesses often fail to provide relief to patients' disruptive and disabling symptoms. Existing and e...
There is mounting evidence suggesting psychedelic and entactogen medicines (namely psilocybin and 3,4-methylenedioxymethamphetamine [MDMA]), in conjunction with proper psychosocial support, hold the potential to provide safe, rapid acting, and robust clinical improvements with durable effects. In the US, both psilocybin and MDMA have been granted Breakthroug...
ContextPeople affected by serious illness usually experience suffering in its various dimensions, not only in the physical but also in the psychosocial and spiritual aspects. The interest in psychedelic-assisted therapies as a potential new therapeutic modality has increased since evidence suggests a significant impact of their use on the outcomes of patient...
“Are magic mushrooms the miracle cure for depression we've been looking for?” (Khan, 2021). Attention-grabbing headlines such as this are becoming increasingly common and suggest that psychedelic medicines are some kind of magic bullet. This perception is increased by stories of people who had a single life-changing psychedelic experience that resulted in co...
The acute subjective effects of psychedelics are responsive to users' expectations and surroundings (i.e., "set and setting"). Accordingly, a great deal of thought has gone into designing the psychosocial context of psychedelic administration in clinical settings. But what theoretical paradigms inform these considerations about set and setting? Here, we desc...
Existential distress is a significant source of suffering for patients facing life-threatening illness. Psychedelic-Assisted Therapies (PAT) are novel treatments that have shown promise in treating existential distress, but openness to providing PAT may be limited by stigma surrounding psychedelics and the paucity of education regarding their medical use. Ho...
Approximately 30% of people treated for a major depressive episode will not achieve remission after two or more treatment trials of first-line antidepressants and are considered to have treatment-resistant depression (TRD). Because the odds of remission decrease with every subsequent medication trial, it is important for clinicians to understand the characte...
The history of research on the use of psychedelic drugs to treat alcohol dependence in the 1950s and 1960s suggests the need for caution in their proposed clinical use. Since 2006 there has been a revival of interest in using psychedelics to treat depression and post-traumatic stress disorders [1] and the addictions [2]. What lessons may we glean from resear...
BackgroundGrowing evidence suggests psilocybin, a naturally occurring psychedelic, is a safe and promising pharmacotherapy for treatment of mood and substance use disorders when administered as part of a structured intervention. In most trials to date, psilocybin dose has been administered on a weight-adjusted basis rather than the more convenient procedure ...
Experiences of intoxication elude scientific research because of their immediate and ‘inner’ nature for the intoxicated individual. In this chapter, we show how ‘trip reports’ - reports of psychedelic intoxication - from online drug information forums and libraries allow for further understanding the experience of psychedelic intoxication from LSD, DMT and p...
The primary objective of this double-blind, placebo-controlled pilot study is to assess the efficacy of psilocybin administration (4-phosphoryloxy-N,N-dimethyltryptamine), a serotonergic psychoactive agent, on psychosocial distress, with the specific primary outcome variable being anxiety associated with cancer. Secondary outcome measures will look at the ef...
Self-administration of very low doses of psychedelic drugs to improve mental health and wellbeing and enhance cognitive function, known as microdosing, has received recent media attention, but little research has been conducted. We conducted a content analysis of discussions about microdosing from the online forum Reddit. We examined motivations, dosing prac...
Meditation and psychedelics have played key roles in humankind's search for self-transcendence and personal change. However, neither their possible synergistic effects, nor related state and trait predictors have been experimentally studied. To elucidate these issues, we administered double-blind the model psychedelic drug psilocybin (315 μg/kg PO) or placeb...
BackgroundDepression and anxiety are prevalent psychiatric disorders that carry significant morbidity. Pharmacological and psychosocial interventions are used to manage these conditions, but their efficacy is limited. Recent interest into the use of psychedelic-assisted therapy using ayahuasca, psilocybin or lysergic acid diethylamide (LSD) may be a promisin...
