Background:
The classical psychedelics, psilocybin, peyote, ayahuasca/N,N-dimethyltryptamine, and lysergic acid diethylamide are considered promising new treatments for psychiatric illnesses, such as ...depression, anxiety, addiction, and obsessive-compulsive disorders. However, their profound and characteristic subjective effects raise concern for distinctive biases in randomized clinical trials.
Methods:
We performed a systematic literature search to identify all clinical trials on classical psychedelics with patient populations to examine descriptive data and determine the risk of bias. Two independent reviewers searched three databases (PubMed, Embase, and APA PsycNet) and extracted information on study design, study population, use of active or inactive placebo, dropouts, evaluation of blinding of intervention, and reporting of expectancy and therapeutic alliance.
Results:
We included 10 papers reporting on 10 unique trials. The trials generally included populations that were predominantly white and highly educated. The trials had small samples and considerable dropout. Blinding was either unsuccessful or not reported regardless of type of placebo. Few trials published protocols, statistical analysis plans (SAPs), and outcomes relating to psychotherapy fidelity. All trials but one were rated as high risk of bias.
Conclusion:
Successful blinding of intervention is a significant challenge in this field. To better accommodate this, we suggest that future trials use a parallel-group design and utilize an active placebo on a psychedelic-naïve population. Future trials should publish trial protocol and SAPs, use clinician-rated outcomes accessed by a blinded rater, evaluate blinding of intervention, and consider measuring expectancy and therapeutic fidelity.
Advocates of the therapeutic use of psychedelic drugs have argued that a promising approach to treatment was prematurely abandoned in the 1960s primarily because of Richard Nixon's 'War on ...Drugs'.This paper (1) briefly describes research in the 1950s and 1960s in North America on the use of LSD to treat alcohol dependence, anxiety in terminal illness, and anxiety and depression; and (2) discusses the factors that led to its abandonment.
An analysis of historical scholarship on psychedelic research in the 1950s, 1960s and 1970s in North America.
Research on psychedelic drugs in psychiatry was abandoned for a number of reasons that acted in concert. A major factor was that clinical research on psychedelic drugs was caught up in the tighter regulation of pharmaceutical research after the Thalidomide disaster in 1963. Psychedelic drugs also presented special challenges for randomised, placebo-controlled clinical trials in the 1970s that were not as positive as the claims made by their advocates in the 1950s and 1960s. Clinical research became more difficult after 1965 when Sandoz ceased providing psychedelic drugs for research and their nonmedical use was prohibited in 1970.
The demise of psychedelic drug research was not solely due to the 'War on Drugs'. It was hastened by tighter regulation of pharmaceutical research, the failure of controlled clinical trials to live up to the claims of psychedelic advocates, and the pharmaceutical industry's lack of interest in funding clinical trials.
Outcomes
1. Discuss advances in psychedelic-assisted therapy science relevant to palliative care settings
2. Explain implications of psychedelic-assisted therapy from myriad disciplinary perspectives ...with the goal of advancing collaboration and the field more broadly
3. Reflect on palliative care practice models as exemplars for relationship-based psychedelic-assisted therapy integration within the health system
In 2021, two landmark randomized controlled studies of psychedelic-assisted therapy generated intense public and scientific interest as well as speculation that MDMA and psilocybin may be granted federal regulatory approval within the next several years for a wide array of mental health indications. Potential applications pertinent to palliative care extend well beyond management of anxiety and depression among those with serious illness to include demoralization, existential distress, grief, meaning making, and life completion.
Unlike other drug therapies where efficacy can be reduced to the biochemical action of the drug, the clinical benefit (or harm) of psychedelic medicines is highly contingent on the mindset of the patient and the physical and emotional setting in which they are used. The quality of presence and skills of the therapist are paramount to establish a trusting relationship and safe environment fostering healing. In many traditions, the therapeutic relationship is considered the “medicine,” and psychedelics act to catalyze and deepen the relational aspects of care that may ease suffering and allow each patient's innate healing processes to unfold.
Training clinicians and therapists skilled in this modality presents a major bottleneck to this developing field and limitation to widespread accessibility, not simply because clinical infrastructure must be converted or developed but because the safety and efficacy of the intervention uniquely depend on the preparation of the clinician. To meet this need, several training programs have developed over the last 5 years. We present a diverse panel of palliative care and hospice clinicians training and working in psychedelic-assisted therapies to share their experiences of training and clinical care and how the interdisciplinary, intensively relationship-centered approach of palliative care may serve as a model for the successful implementation of psychedelic medicines more broadly across society.
•Illicit drugs seized by police were mainly methamphetamine, MDMA and cocaine.•Cocaine, 2C-B and GHB were more frequently adulterated with other substances.•Methamphetamine, MDMA, THC and heroin ...samples showed high purity.•Methamphetamine and MDMA contained also the largest variety of impurities.•Emerging NPS as adulterants are similar to that reported in Europe.
Impurities in commonly used illicit drugs raise concerns for unwitting consumers when pharmacologically active adulterants, especially new psychoactive substances (NPS), are used. This study examines impurities detected in illicit drugs seized in one Australian jurisdiction.
Queensland Health Forensic and Scientific Services provided analytical data. Data described the chemical composition of 9346 samples of 11 illicit drugs seized by police during 2015-2016. Impurities present in primary drugs were summarized and tabulated. A systematic search for published evidence reporting similar analyses was conducted.
Methamphetamine was the primary drug in 6608 samples, followed by MDMA (1232 samples) and cocaine (516 samples). Purity of primary drugs ranged from ∼30% for cocaine, 2-CB and GHB to >90% for THC, methamphetamine, heroin and MDMA. Methamphetamine and MDMA contained the largest variety of impurities: 22 and 18 variants, respectively. Drug adulteration patterns were broadly similar to those found elsewhere, including NPS, but in some primary drugs impurities were found which had not been reported elsewhere. Psychostimulants were adulterated with each other. Levamisole was a common impurity in cocaine. Psychedelics were adulterated with methamphetamine and NPS. Opioids were quite pure, but some samples contained methamphetamine and synthetic opioids.
Impurities detected were mostly pharmacologically active adulterants probably added to enhance desired effects or for active bulking. Given the designer nature of these drug cocktails, the effects of the adulterated drugs on users from possible complex multi-drug interactions is unpredictable. Awareness-raising among users, research into complex multi-drug effects and ongoing monitoring is required.
PsyBio Therapeutics is poised to fully develop a cost competitive solution for human clinical testing of these tryptamine therapeutic candidates as new chemical entities possessing key advantages ...over current in-clinic treatments for a range of mental health conditions impacting roughly 1 billion people globally.KEY FACTS: Globally, individuals with untreated mental health conditions have a median life expectancy that is approximately 10 years shorter than mentally healthy individuals. Recombinant psilocybin biosynthesis was first reported in 2018 in Aspergillus nidulans, followed by the first bacterial biosynthesis in Escherichia coli in 2019 and a 2020 study in Saccharomyces cerevisiae.Acknowledgments Figure is created with BioRender.com.Declaration of interests J.A.J. is the chairman of the scientific advisory board and a significant stakeholder at PsyBio Therapeutics.
Do psychedelics affect sexual functioning postacutely? Anecdotal and qualitative evidence suggests they do, but this has never been formally tested. While sexual functioning and satisfaction are ...generally regarded as an important aspect of human wellbeing, sexual dysfunction is a common symptom of mental health disorders. It is also a common side effect of selective serotonin reuptake inhibitors (SSRIs), a first line treatment for depression. The aim of the present paper was to investigate the post-acute effects of psychedelics on self-reported sexual functioning, combining data from two independent studies, one large and naturalistic and the other a smaller but controlled clinical trial. Naturalistic use of psychedelics was associated with improvements in several facets of sexual functioning and satisfaction, including improved pleasure and communication during sex, satisfaction with one's partner and physical appearance. Convergent results were found in a controlled trial of psilocybin therapy versus an SSRI, escitalopram, for depression. In this trial, patients treated with psilocybin reported positive changes in sexual functioning after treatment, while patients treated with escitalopram did not. Despite focusing on different populations and settings, this is the first research study to quantitively investigate the effects of psychedelics on sexual functioning. Results imply a potential positive effect on post-acute sexual functioning and highlight the need for more research on this.
Background:
Research with the Psychedelic Experience Questionnaire/Scale (PES) focuses on questions relating to mystical experience (Mystical Experience Questionnaire (MEQ)). The psychometric ...potential of the non-MEQ items of the PES remains largely unexplored.
Aims:
We investigated whether the PES also yields subscales besides the MEQ30 subscales.
Methods:
Data from 239 PES measurements (140 healthy participants) from six studies with moderate to high doses of lysergic acid diethylamide and/or psilocybin were included. New subscales (with items other than MEQ30) were created and validated as follows: (1) theoretical derivation of candidate items; (2) removal of items with rare experiences; (3) exploratory factor analysis; and (4) confirmatory factor analysis. Correlations of subscales within the PES and between the PES and the 5-Dimensional Altered States of Consciousness Scale (5D-ASC) were performed. In addition, a cluster analysis using all items (except rare experiences) was performed.
Results:
The reliability of the four original factors of the MEQ30 was confirmed and four additional factors for the non-MEQ items were revealed: paradoxicality, connectedness, visual experience, and distressing experience. The first two additional factors were strongly correlated with the MEQ30 mystical subscale. Adding the new subscales to the MEQ30 subscales increased the explained variance with the 5D-ASC. The cluster analysis confirmed our main results and provided additional insights for future psychedelic psychometrics.
Conclusion:
The study yields a new validated 6-factor structure for extended mystical experience (MEQ40: MEQ30 + Paradoxicality + Connectedness) and covers psychedelic experience as a whole more comprehensively than has hitherto been possible within a single questionnaire (PES48). The entire PES (PES100) can also be used for further future psychedelic-psychometric research.
Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are potent psychoactive ...substances that have been studied for their physiological and psychological effects. However, our understanding of the potential interactions and outcomes when using these substances in combination with other drugs is limited. This systematic review aims to provide a comprehensive overview of the current research on drug–drug interactions between classic psychedelics and other drugs in humans. We conducted a thorough literature search using multiple databases, including PubMed, PsycINFO, Web of Science and other sources to supplement our search for relevant studies. A total of 7102 records were screened, and studies involving human data describing potential interactions (as well as the lack thereof) between classic psychedelics and other drugs were included. In total, we identified 52 studies from 36 reports published before September 2, 2023, encompassing 32 studies on LSD, 10 on psilocybin, 4 on mescaline, 3 on DMT, 2 on 5-MeO-DMT and 1 on ayahuasca. These studies provide insights into the interactions between classic psychedelics and a range of drugs, including antidepressants, antipsychotics, anxiolytics, mood stabilisers, recreational drugs and others. The findings revealed various effects when psychedelics were combined with other drugs, including both attenuated and potentiated effects, as well as instances where no changes were observed. Except for a few case reports, no serious adverse drug events were described in the included studies. An in-depth discussion of the results is presented, along with an exploration of the potential molecular pathways that underlie the observed effects.
Mental health problems constitute a major issue in contemporary society. Meanwhile, the evidence of the therapeutic potential of psychedelics obtained in clinical trials is continuing to grow. One of ...the remarkable characteristics of this class of substances is the fact that they appear to be effective in the treatment of a variety of psychological symptoms and mental illnesses across diagnostic categories. Psychedelics thus seem to have a wider range of usefulness than traditional psychopharmaceuticals, which generally tend to target specific symptoms. The administration of psychedelics includes the presence of an experienced professional until the acute effects subside. Moreover, these substances should be administered as part of a broader, more comprehensive programme, including preparatory and follow-up sessions. Psychedelic therapy can also have an effect on certain psychological phenomena and processes even in healthy volunteers, e.g. increase their well-being, openness, mindfulness capacities and mental flexibility. These phenomena are important correlates of mental health. The available evidence seems to indicate that the key psychological mechanism of the therapeutic effect of psychedelics is their impact on psychological flexibility. This could be the common underlying factor explaining the therapeutic efficacy of psychedelics in the treatment of various mental health disorders across diagnostic categories. The transdiagnostic nature of this mechanism suggests that psychedelic therapy could potentially prove useful, apart from the treatment of various pathologies, also as a tool for general mental health promotion and prevention of mental illness in healthy people. Psychedelic therapy brings the attention to the multifactorial etiology of mental disorders, the importance of the psychotherapy component in healthcare, and the role of transdiagnostic processes and non-pharmacological variables. In this review article, the potential of psychedelics in mental health care, their mechanisms of action, and possible risks as well as risk-prevention strategies is discussed.
This study invited providers who care for patients with eating disorders to inform engagement, communication, and collaboration with psilocybin-assisted psychotherapy interventions.
Medical and ...mental health providers who treat patients with eating disorders were recruited via professional referral networks and participant driven sampling from across California to participate in one of five focus groups. Discussion topics included prior knowledge of psychedelic therapy, interest/concerns related to psilocybin therapy, and opportunities for collaboration. Study team members completed iterative rounds of coding with a grounded theory approach.
A total of 32 participants reported a range of familiarity with psychedelics. Some raised concerns about the risks of administering psilocybin to malnourished patients and to those with psychological comorbidities. Despite these concerns, participants were hopeful to see psilocybin therapy as a treatment for patients with eating disorders. In anticipating challenges, providers had concerns about equity in access to care among publicly insured and non-English speaking patients. They requested opportunities for continuing education about psilocybin therapy.
Our findings demonstrate provider interest in psilocybin therapy for the treatment of patients with eating disorders. As psilocybin therapy interventions are developed, providers caring for patients with eating disorders value collaboration to improve longitudinal patient outcomes.
This study invited healthcare providers of patients with eating disorders to discuss their thoughts around the use of psilocybin-assisted psychotherapy in this population. Findings will help inform emerging psilocybin therapy clinical trials with the goal of successful translation and adoption in real world clinical settings.
