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![Weekly topics and goals of MCP sessions [21]](publication/378150291/figure/tbl1/AS:11431281223379877@1707757557498/Weekly-topics-and-goals-of-MCP-sessions-21_Q320.jpg)
Background
An advanced cancer diagnosis can be associated with a significant profile of distress. Psychedelic compounds have shown clinically significant effects in the treatment of psychological distress in patients with advanced-stage cancer. Given the challenges of delivering timely and effective intervention in the advanced cancer context, it i...
Contexts in source publication
Context 1
... addition, the investigator may discontinue a participant from the trial at any time if the Investigator considers it necessary for any reason including patient death, eligibility violations, significant non-compliance with treatment or trial requirements, an adverse event or medical condition requiring discontinuation, withdrawal of consent, or loss to follow-up. Significant non-compliance is where a participant falls below feasibility criteria (see Table 4) without having a justifiable health or cancer treatment-related reason. ...Context 2
... and secondary outcome measures are outlined in Tables 4 and 5. Feasibility measures include adherence to medication regimen, attendance at MCP sessions, MCP treatment fidelity, and participant recruitment and attrition rates; the feasibility targets (detailed below) are based on previous research [21,22]. ...Similar publications
Psychedelics are serotonergic drugs that profoundly alter consciousness, yet their neural mechanisms are not fully understood. A popular theory, RElaxed Beliefs Under pSychedelics (REBUS), posits that psychedelics flatten the hierarchy of information flow in the brain. Here, we investigate hierarchy based on the imbalance between sending and receiv...
The pharmacodynamic effects of lysergic acid diethylamide (LSD) are diverse and different in different individuals. Effects of other psychoactive substances have been shown to be critically influenced by non-pharmacological factors such as personality traits and mood states. The aim of this study was to determine pharmacological and psychological p...
Background
Anxiety disorders are a major public health burden with limited treatment options.
Aims
We investigated the long-term safety and efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with anxiety with or without life-threatening illness.
Method
This study was an a priori -planned long-term follow-up of an investigat...
Introduction
Lysergic acid diethylamide (LSD) and 3,4 Methylenedioxymethamphetamine (MDMA) are widely used psychoactive drugs and their potential use in psychiatric medicine is currently generating interest. The mechanism by which these drugs may assist recovery in addiction, mood disorders and post-traumatic stress disorder (PTSD) is still not wel...
Purpose of Review
Serotonergic psychedelics include psilocybin, lysergic acid diethylamide (LSD), dimethyltryptamine (DMT), and other agonists of the 5-HT2A receptor. While the efficacy and safety of psychedelics for depression have shown promising initial results in clinical trials, there is much to understand regarding how these effects occur. Th...
Citations
... While clinical trials on LSD microdosing are ongoing (Donegan et al., 2023;Daldegan-Bueno et al., 2024;Wells et al., 2024), animal research has the potential to provide valuable insights into two important aspects: (1) demonstrate whether microdosing can elicit detectable behavioral changes within animal models, thereby supporting the claim that the reported effects of microdosing are not merely a placebo response, and (2) assess safety and tolerability associated with chronic use. ...
Microdosing, the repeated use of psychedelic substances at low doses, is growing in popularity among recreational consumers. While this practice is associated with many benefits to mood, well-being and health, research in this area is in its early stages and predominantly centered on human applications. In this narrative review, we synthesize the findings from studies investigating the effects of microdosing on the behaviors of three animal species: rats, mice, and zebrafish. A total of 12 studies were identified that implemented a microdosing regimen of LSD, psilocybin, or DMT in these animal models. Overall, microdosing caused little changes in behaviors associated with anxiety- and depressive-like states. Moreover, while microdosing was well-tolerated across species, further research is needed to capture specific safety concerns. Finally, we critically appraise the studies included in this review based on their methodologies and discuss further avenues of research to advance the preclinical literature on psychedelic microdosing. Specifically, we recommend that future research prioritize the replication of existing findings to inform the development of robust study designs and dosing protocols, as well as establish standardized methodologies to enable effective comparisons across different animal models. Furthermore, future investigations should explore the therapeutic potential of mescaline microdosing, examine sex-dependent effects, and extend research to additional models of psychiatric conditions, including those related to obsessive-compulsive disorder and post-traumatic stress disorder.
... Based on these phase IIa results, several phase IIb studies in MDD (ACTRN12624000128594), cancer patients with existential distress/depression (ACTRN12623000478617) [103], premenstrual syndrome, and pre-menstrual syndrome/pre-menstrual dysphoric disorder are underway. The protocol of the ACTRN12624000128594 trials has been published, with a dosing range from 4 to 20 µg per dosing day [104]. ...
Objective: To narratively review currently available antidepressants and future potential antidepressants as monotherapy for the treatment of depressive disorders. Methods: Selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), dopamine reuptake inhibitor (bupropion), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs) were reviewed according to the results from Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study and systematic reviews. For the rest of the antidepressants, a PubMed/Medline search was conducted with priority for systematic reviews. For drugs in development for depressive disorders, PubMed, Google, and Clinicaltrials.gov databases were used. Results: The STAR*D Study demonstrated that sertraline, venlafaxine, and bupropion monotherapy had similar efficacy in patients with major depressive disorder (MDD) who failed citalopram. A network meta-analyses of randomized, placebo-controlled trials found that SSRIs, SNRIs, bupropion, TCAs, mirtazapine, and agomelatine had similar relative efficacy compared to placebo, but had different acceptability. Gepirone had more failed/negative studies and smaller effect size relative to placebo compared to other antidepressants. The combination of dextromethorphan and bupropion, ketamine infusion, and intranasal esketamine had faster onset of action but similar effect size compared to monoamine-based antidepressants as monotherapy. Brexanolone and zuranolone are effective in postpartum depression (PPD), but the effect size of zuranolone in MDD as monotherapy or adjunctive therapy was very small. Psychedelics, glutamate receptor-related agents, kappa opioid receptor antagonists, orexin receptor antagonists, new anti-inflammatory agents, and biomarker-based antidepressant therapy have been under investigation for depressive disorders. Psychedelics showed faster onset of action, large effect size, and long durability. Conclusions: Monoamine-based antidepressants likely continue to be the mainstream antidepressants for depressive disorder. NMDA receptor antagonists and neurosteroid antidepressants will play a bigger role with the improvement of accessibility. Psychedelics may become a game changer if phase III studies validate their efficacy and safety in depressive disorders.
... There are several clinical trials currently investigating PAT in Aotearoa [13][14][15] and, as such, it is a timely priority to include a Māori voice in the development of such interventions. This requires understanding the views of Māori healthcare professionals, given that they are key stakeholders in the development and delivery of such interventions and would become referrers and/or providers of PAT should it become available. ...
... 25 Benefits of microdosing are commonly reported in observational research, though rigorous experimental evidence is still underway. 14,15,[26][27][28] Despite this, anecdotal reports and media attention combined with the growing body of evidence for macrodose interventions may have contributed to reduced risk perception of LSD and other psychedelic substances, leading to an uptick in naturalistic use with therapeutic intention. 29 Though psychedelics have a good safety profile, some naturalistic users may be unaware of potential risks, including psychiatric or physical risk factors and variability in drug purity and dosage. ...
aim: Psychedelic-assisted therapies are gaining interest as an innovative treatment for problems with mental health and addictions, and there are several clinical trials in this area currently being conducted in Aotearoa New Zealand. However, many stakeholder groups hold concerns about cultural acceptability and safety. While psychedelic substances have a long history overseas in various Indigenous populations for spiritual and ritualistic purposes, their traditional use with Māori in Aotearoa New Zealand is unclear. Given our Te Tiriti o Waitangi obligations and the significant health inequities for Māori, any new treatments should be developed considering Te Ao Māori (Māori worldview) perspectives. This study aimed to explore Māori healthcare professionals’ current awareness, attitudes and perspectives on psychedelics and psychedelic-assisted therapy. methods: To explore these aims, 13 Māori healthcare professionals were recruited to participate in semi-structured qualitative interviews investigating psychedelic awareness, knowledge and attitudes using Māori health models Te Whare Tapa Whā and Te Wheke as a framework for data collection and analysis. results: Four key themes were identified, including 1) greater awareness leads to greater openness towards psychedelic-assisted therapy (PAT), 2) more research and education about PAT is needed, 3) PAT has the potential to align with Te Ao Māori, and 4) equitable access is critical for Māori. conclusion: Our sample of Māori healthcare professionals generally supported research investigating psychedelic therapies in Aotearoa New Zealand. Improving awareness of this novel treatment is likely to influence its acceptability as a treatment option and will inform the cultural safety of its use with Māori.
... [17][18][19]21,22,24,27,36,42,44,45 Some focused on 3,4-methylenedioxymethamphetamine-assisted therapy (n = 1), 25 ketamine-assisted therapy (n = 1), 47 and lysergic acid diethylamide-assisted therapy (n = 1). 26 Others focused on multiple psychedelic substances. 2,8,14,20,23,[28][29][30][31][32]34,35,[37][38][39][40][41]43,48 ...
... Participants in PAT trials were screened using a comprehensive set of inclusion and exclusion criteria that were developed by each study team. 19,[24][25][26] Inclusion criteria varied yet often required some level of baseline distress associated with life-threatening illness, diagnosis of a serious or incurable illness (such as cancer), life expectancy > 3 months, and willingness to refrain from medications or activities that could impede the safety of the intervention. 19,[24][25][26] Exclusion criteria often addressed comorbidities that posed safety risks in the context of PAT, such as liver dysfunction, certain cardiovascular conditions, uncontrolled psychiatric comorbidities, or active suicidality. ...
... 19,[24][25][26] Inclusion criteria varied yet often required some level of baseline distress associated with life-threatening illness, diagnosis of a serious or incurable illness (such as cancer), life expectancy > 3 months, and willingness to refrain from medications or activities that could impede the safety of the intervention. 19,[24][25][26] Exclusion criteria often addressed comorbidities that posed safety risks in the context of PAT, such as liver dysfunction, certain cardiovascular conditions, uncontrolled psychiatric comorbidities, or active suicidality. 19,[24][25][26] Preparation All studies included an informed consent process that involved discussion of PAT, as well as potential benefits and risks. ...
Psychedelic-assisted therapy (PAT) involves supported experiences with psychedelic medicines in carefully curated environments. Early evidence suggests possible utility of PAT for addressing psychosocial-spiritual-existential concerns, yet gaps remain in understanding findings related to PAT's role in palliative care. This rapid review aims to synthesize current literature on applications of PAT in the context of palliative care. Through a systematic process, we identified 34 articles published between January 2021 and July 2024. Protocols varied yet included common components of participant screening, preparation, dosing, and integration. Psilocybin was the most commonly studied compound. Results support safety and initial efficacy of PAT for psycho-spiritual-existential outcomes among carefully screened and highly homogonous samples of patients with serious illness (predominantly cancer). Current efforts and challenges around integrating PAT into systems of palliative care were highlighted. Additional work is needed to (1) explore PAT's safety and efficacy within more diverse samples and contexts, (2) train palliative care providers on PAT, (3) determine systems of care delivery best suited for translation of PAT into practice, and (4) begin developing policy solutions to support safe and equitable access to PAT. Because many patients lack access to basic psychosocial-spiritual-existential care, careful consideration is needed around integration of PAT.
The psychedelic substances which are the topic of this article are not currently FDA approved for use in the United States.
... Most studies have been conducted in controlled clinical settings, typically involving preparatory sessions, the administration of psilocybin under supervision, and integration sessions afterwards. Participants were generally patients with advanced or terminal cancer diagnoses experiencing anxiety, depression, or existential distress related to their condition [75][76][77][78]. For example, a pilot study at the University of California, Los Angeles, reignited interest in psilocybin treatment for advanced-stage cancer patients, leading to renewed efforts in psilocybin research [58]. ...
Simple Summary
Psilocybin therapy shows promise for reducing anxiety and depression and improving psychological well-being in cancer patients nearing the end of life. However, providing this treatment outside of tightly controlled research studies is extremely challenging. In 2020, Oregon became the first U.S. state to legalize psilocybin therapy for depression related to terminal illnesses such as advanced cancer. This review examines the published evidence on psilocybin’s therapeutic potential as well as the multitude of legal, ethical, and logistical hurdles Oregon has faced while attempting to roll out regulated psilocybin services over the past year. The aim is to shed light on the complex issues involved in responsibly implementing psychedelic-assisted therapy for patient populations with serious psychological distress. By proactively identifying and addressing these challenges, appropriate standards of care and equitable access to psilocybin treatment can be ensured as it transitions from research to real-world clinical practice. Insights from Oregon’s experience as the pioneering state can help guide a rigorous, ethical path forward.
Abstract
Despite the legalization of psilocybin therapy for depression in terminal illnesses such as advanced cancer through Oregon’s Measure 109 in 2020, significant challenges have impeded its implementation. This review synthesizes the empirical data supporting the utilization of psilocybin therapy for addressing cancer-related depression, including an evaluation of its purported benefits and potential adverse effects. It provides a comprehensive examination of therapeutic strategies, dosing regimens, and barriers to ensuring responsible and equitable access. Salient issues explored include the development of ethical protocols, integration within healthcare systems, ensuring statewide availability, resolving legal ambiguities, and defining clinical standards. Oregon’s pioneering role serves as a case study, highlighting the necessity of addressing regulatory, logistical, and ethical obstacles to ensure the establishment of rigorous and equitable psilocybin care models.
