Developing an Ethics and Policy Framework for Psychedelic Clinical Care: A Consensus Statement.

Importance: As government agencies around the globe contemplate approval of the first psychedelic medicines, many questions remain about their ethical integration into mainstream medical practice. Objective: To identify key ethics and policy issues related to the eventual integration of psychedelic therapies into clinical practice. Evidence Review: From June 9 to 12, 2023, 27 individuals representing the perspectives of clinicians, researchers, Indigenous groups, industry, philanthropy, veterans, retreat facilitators, training programs, and bioethicists convened at the Banbury Center at Cold Spring Harbor Laboratory. Prior to the meeting, attendees submitted key ethics and policy issues for psychedelic medicine. Responses were categorized into 6 broad topics: research ethics issues; managing expectations and informed consent; therapeutic ethics; training, education, and licensure of practitioners; equity and access; and appropriate role of gatekeeping. Attendees with relevant expertise presented on each topic, followed by group discussion. Meeting organizers (A.L.M., I.G.C., D.S.) drafted a summary of the discussion and recommendations, noting points of consensus and disagreement, which were discussed and revised as a group. Findings: This consensus statement reports 20 points of consensus across 5 ethical issues (reparations and reciprocity, equity, and respect; informed consent; professional boundaries and physical touch; personal experience; and gatekeeping), with corresponding relevant actors who will be responsible for implementation. Areas for further research and deliberation are also identified. Conclusions and Relevance: This consensus statement focuses on the future of government-approved medical use of psychedelic medicines in the US and abroad. This is an incredibly exciting and hopeful moment, but it is critical that policymakers take seriously the challenges ahead.

Clinical Research Trials of Psychedelic-Assisted Therapy in Adolescents Aged 16 to 17 Years: Rationale Balanced With Caution.

Youth today are burdened by significant mental health challenges. In 2022, 25% of adolescents aged 12 to 17 years experienced a mental illness, with 20% experiencing a depressive episode, 12.5% reporting serious thoughts of suicide, and 17% meeting criteria for a substance use disorder.1 Close to 5% of adolescents experience posttraumatic stress disorder.2 Impairing psychiatric symptoms remain present in upwards of 40% of adolescents after receiving existing mental health services,3 so it is necessary to identify additional and more effective treatment options. We propose there is an acceptable benefit-to-risk calculation that supports trialing classic serotonergic psychedelics (eg, psilocybin) and phenethylamine compounds with empathogenic and entactogenic range of effects (eg, 3,4-methylenedioxymethamphetamine [MDMA]) in combination with psychotherapy among select adolescents aged 16 to 17 years. Specifically, we propose testing these treatments among adolescents aged 16 to 17 years who are experiencing treatment-resistant manifestations of psychiatric disorders (ie, multiple failed trials of current evidence-based treatments) or psychiatric disorders that are in line with the current evidence base for adults as determined, for example, by the breakthrough designation of the US Food and Drug Administration for a particular psychedelic medicine (eg, psilocybin for major depressive disorder, MDMA for posttraumatic stress disorder).

Psychedelic Science, Contemplative Practices, and Indigenous and Other Traditional Knowledge Systems: Towards Integrative Community-Based Approaches in Global Health.

As individuals and communities around the world confront mounting physical, psychological, and social threats, three complimentary mind-body-spirit pathways toward health, wellbeing, and human flourishing remain underappreciated within conventional practice among the biomedical, public health, and policy communities. This paper reviews literature on psychedelic science, contemplative practices, and Indigenous and other traditional knowledge systems to make the case that combining them in integrative models of care delivered through community-based approaches backed by strong and accountable health systems could prove transformative for global health. Both contemplative practices and certain psychedelic substances reliably induce self-transcendent experiences that can generate positive effects on health, well-being, and prosocial behavior, and combining them appears to have synergistic effects. Traditional knowledge systems can be rich sources of ethnobotanical expertise and repertoires of time-tested practices. A decolonized agenda for psychedelic research and practice involves engaging with the stewards of such traditional knowledges in collaborative ways to codevelop evidence-based models of integrative care accessible to the members of these very same communities. Going forward, health systems could consider Indigenous and other traditional healers or spiritual guides as stakeholders in the design, implementation, and evaluation of community-based approaches for safely scaling up access to effective psychedelic treatments.

The Safety and Efficacy of Psychedelic-Assisted Therapies for Older Adults: Knowns and Unknowns.

Psychedelics and related compounds have shown efficacy for the treatment of a variety of conditions that are prevalent among older adults, including mood disorders, the psychological distress associated with a serious medical illness, post-traumatic stress disorder (PTSD), and prolonged grief disorder. Psychedelics also have properties that could help provide therapeutic benefits for patients with dementing disorders, as well as promoting personal growth among healthy older adults. This article focuses on psilocybin, a classic psychedelic, and MDMA, a substituted amphetamine with properties similar to classic psychedelics. Both act on the 5HT2A receptor. Psychedelics can be safely administered to healthy adults in controlled conditions. However, both psilocybin and MDMA can increase blood pressure and heart rate, which could be a concern if used in older adults with cardiovascular disease. Very few older adults or patients with serious comorbidities have been included in clinical trials of psychedelics to date, raising the question of how generalizable study results are for the patients that most geropsychiatrists will be treating. Research on the neurophysiologic and mechanistic effects of psychedelics in older adults could also provide insights into the aging brain that could have clinical applications in the future. Given the potential of psychedelic compounds to benefit older adults, more research is needed to establish safety and efficacy among older adults, particularly those with multi-morbidity.

Anterior Cruciate Ligament Reconstruction Using Bone-Patella Tendon-Bone Autograft With Press-Fit Femoral Fixation: The Original Chambat Technique.

Patellar tendon grafts have long been considered the gold standard for anterior cruciate ligament reconstruction (ACLR). This Technical Note describes ACLR using bone-patella tendon-bone (BPTB) autograft with press-fit femoral fixation using an outside-in drilling technique.

Policy considerations that support equitable access to responsible, accountable, safe, and ethical uses of psychedelic medicines.

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 Breakthrough Therapy designations by the US Food and Drug Administration and may potentially receive full FDA approval with similar regulatory considerations occurring in multiple countries. At the same time, regulatory changes are poised to increase access to legal or decriminalized psychedelic use in various non-medical settings. This review provides a brief discussion on the historical use of psychedelic medicines, the status of the empirical evidence, and numerous significant policy considerations that must be thoughtfully addressed regarding standards-of-practice, consumer protection, engagement of communities, safeguarding access for all, and developing data standards, which supports the responsible, accountable, safe, and ethical uses of these medicines in clinical, faith-based, and other contexts. We provide suggestions for how public health and harm reduction can be supported through a public-private partnership that engages a community of stakeholders from various disciplines in the co-creation and dissemination of best practices and public policies.

All-Arthroscopic Treatment of Combined Posterior Cruciate Ligament and Posterolateral Corner Instability.

Injuries to the posterolateral corner (PLC) of the knee are uncommon, and usually associated with other ligamentous injuries. A combined posterior cruciate ligament (PCL) and PLC tear is the most frequent combination. Several studies describe anatomic reconstructive techniques using an open approach with large incisions and extensive exploration of the posterolateral structures. This Technical Note describes an all-arthroscopic technique as a safe and efficient treatment of combined PCL and PLC instability using the trans-septal approach.

If the Doors of Perception Were Cleansed, Would Chronic Pain be Relieved? Evaluating the Benefits and Risks of Psychedelics.

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 transcendence. Over the past 2 decades, there has been increasing interest in psychedelics as treatments for various medical disorders, including chronic pain. Although concerns about adverse medical and psychological effects contributed to their controlled status, contemporary knowledge of psychedelics suggests that risks are relatively rare when patients are carefully screened, prepared, and supervised. Clinical trial results have provided support for the effectiveness of psychedelics in different psychiatric conditions. However, there are only a small number of generally uncontrolled studies of psychedelics in patients with chronic pain (eg, cancer pain, phantom limb pain, migraine, and cluster headache). Challenges in evaluating psychedelics as treatments for chronic pain include identifying neurobiologic and psychosocial mechanisms of action and determining which pain conditions to investigate. Truly informative proof-of-concept and confirmatory randomized clinical trials will require careful selection of control groups, efforts to minimize bias from unblinding, and attention to the roles of patient mental set and treatment setting. PERSPECTIVE: There is considerable promise for the use of psychedelic therapy for pain, but evidence-based recommendations for the design of future studies are needed to ensure that the results of this research are truly informative.

Suture Hook Versus All-Inside Repair for Longitudinal Tears of the Posterior Horn of the Medial Meniscus Concomitant to Anterior Cruciate Ligament Reconstruction: A Matched-Pair Analysis From the SANTI Study Group.

BACKGROUND: Secondary meniscectomy rates after repair of longitudinal tears of the posterior horn of the medial meniscus (PHMM) performed concomitantly with anterior cruciate ligament reconstruction (ACLR) are reported to be as high as 25% with an all inside repair technique. Posteromedial portal suture hook repair is an emerging technique; however, it is unknown whether it confers a significantly reduced secondary meniscectomy rate compared with the current gold standard. PURPOSE/HYPOTHESIS: The primary objective of this study was to compare the secondary meniscectomy rates of suture hook repair and all inside repair for longitudinal tears of the PHMM performed concomitant to ACLR. The secondary outcome was to determine the risk factors associated with the failure of the repair. It was hypothesized that repair with an all inside device would be associated with higher secondary meniscectomy rates when compared with suture hook repair and that concomitant anterolateral ligament reconstruction (ALLR) would confer improved meniscal repair survivorship. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients with longitudinal tears of the PHMM who underwent meniscal repair during primary ACLR between January 2011 and December 2015 at our institution were eligible for the study. Patients undergoing suture hook repair were propensity matched in a 1:1 ratio to patients who underwent all inside repair. At the end of the study period, secondary meniscectomy rates were determined. RESULTS: The study population comprised 237 matched pairs. The mean follow up was 97.7 ± 17.3 months. Patients who underwent an all inside repair had a >2-fold higher failure rate compared with patients who underwent suture hook repair through a posteromedial portal (31.2% vs 15.6%; P = .0003). Patients in the suture hook repair group undergoing additional ALLR demonstrated a >3-fold higher meniscal repair survival rate compared with all other subgroups (P = .0014). This association was not seen in the all inside repair group. The only statistically significant risk factor for meniscal repair failure was the suture repair technique (hazard ratio, 2.133 [95% CI, 1.383-3.292]; P = .0008). CONCLUSION: Suture hook repair through a posteromedial portal is associated with a significantly lower secondary meniscectomy rate when compared with the all inside meniscal repair of longitudinal tears of the PHMM performed at the time of ACLR. Furthermore, patients in the suture hook repair group who underwent an additional ALLR had a significantly better meniscal repair survivorship compared with all other subgroups.

How to Avoid Iatrogenic Saphenous Nerve Injury During Outside-In or Inside-Out Medial Meniscus Sutures.

Medial meniscal sutures using outside-in or inside-out techniques are very popular. Nevertheless, a saphenous nerve entrapment may occur with these techniques. This Technical Note describes a modified outside-in medial meniscus suture without any additional skin incisions. By dissecting the space between the subcutaneous and the capsule, which is performed by grasping and knotting the sutures through the anteromedial portal, iatrogenic saphenous nerve injury is avoided.

Challenges in translational research: MDMA in the laboratory versus therapeutic settings.

Despite substantial progress in the use of mind-altering drugs to treat psychiatric disorders, the psychological processes through which these drugs change mood or behavior are poorly understood. Controlled laboratory studies with well-defined psychological constructs are valuable to understand how these drugs manifest their therapeutic benefit. However, there are substantial methodological differences between clinical studies investigating therapeutic outcome and laboratory studies investigating the processes that might underlie the therapeutic effects. Here, we examine some of these differences using the example of 3,4-methylenedioxymethamphetamine (MDMA). We review differences in expectancies, social and physical context, participant characteristics, pharmacological factors, and outcome measures in studies with participants who do or do not have psychiatric diagnoses. We describe the challenges and opportunities in translating findings from laboratory studies to the clinic and identify ways to bridge the gap between these approaches.

Arthroscopy training in France: A resident perception and self-assessment.

BACKGROUND: Arthroscopic surgery is a steadily expanding component of orthopaedic practice that changes continuously as new techniques and indications develop. The many arthroscopy training activities offered to residents include fellowships, practice on cadaver specimens and simulators, and teaching in the operating room. Current practices for arthroscopy training of orthopaedic residents in France have not yet been evaluated. The objectives of this study were to describe current arthroscopy training practices and to assess the perceptions and expectations of residents and junior physicians in France, in order to contribute to the development of a new training strategy for residents. HYPOTHESIS: Residents and junior physicians perceive gaps in their arthroscopy training. METHODS: Between November 2018 and February 2019, the Junior French Arthroscopy Society (Société Francophone d'Arthroscopie Junior, SFAJ) conducted a descriptive epidemiological survey of 918 residents, clinical fellows, and junior physicians in orthopaedic surgery departments in France. The data were collected via an online questionnaire sent by e-mail. The questionnaire had items on demographics; perceptions of, and expectations about, arthroscopy skills training during the residency; and experience in performing arthroscopic procedures. RESULTS: Of the 918 residents, 106 responded to the questionnaire. Most respondents were near the end of their training: 26 (24.8%) were 4th-year residents, 23 (21.6%) were 5th-year residents, 15 (14.3%) were clinical fellows, and 13 (12.4%) were junior physicians. Among respondents, 42 (40%) had performed fewer than 5 simple arthroscopy procedures as the main operator and 73 (69.5%) felt they were not, or would not be, capable of performing arthroscopic procedures without supervision by the end of their residency. CONCLUSION: The survey findings highlighted the challenges encountered by French orthopaedics residents in acquiring satisfactory arthroscopy skills during their residency. They also suggested avenues for improvement such as simulator training or the development of training on cadaver specimens. LEVEL OF EVIDENCE: IV, descriptive survey.

Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study.

RATIONALE: Standard therapeutic approaches to reduce social anxiety in autistic adults have limited effectiveness. Since 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy shows promise as a treatment for other anxiety disorders, a blinded, placebo-controlled pilot study was conducted. OBJECTIVES: To explore feasibility and safety of MDMA-assisted psychotherapy for reduction of social fear and avoidance that are common in the autistic population. METHODS: Autistic adults with marked to very severe social anxiety were randomized to receive MDMA (75 to 125 mg, n = 8) or inactive placebo (0 mg, n = 4) during two 8-h psychotherapy sessions (experimental sessions) in a controlled clinical setting. Double-blinded experimental sessions were spaced approximately 1 month apart with 3 non-drug psychotherapy sessions following each. The primary outcome was change in Leibowitz Social Anxiety Scale (LSAS) Total scores from Baseline to one month after the second experimental session. Outcomes were measured again six months after the last experimental session. RESULTS: Improvement in LSAS scores from baseline to the primary endpoint was significantly greater for MDMA group compared to the placebo group (P = 0.037), and placebo-subtracted Cohen's d effect size was very large (d = 1.4, CI - 0.074, 2.874). Change in LSAS scores from baseline to 6-month follow-up showed similar positive results (P = 0.036), with a Cohen's d effect size of 1.1 (CI - 0.307, 2.527). Social anxiety remained the same or continued to improve slightly for most participants in the MDMA group after completing the active treatment phase. CONCLUSIONS: This pilot trial demonstrated rapid and durable improvement in social anxiety symptoms in autistic adults following MDMA-assisted psychotherapy. Initial safety and efficacy outcomes support expansion of research into larger samples to further investigate this novel treatment for social anxiety. TRIAL REGISTRATION: clinicaltrials.gov identifier, NCT02008396.

Is LSD toxic?

LSD (lysergic acid diethylamide) was discovered almost 75 years ago, and has been the object of episodic controversy since then. While initially explored as an adjunctive psychiatric treatment, its recreational use by the general public has persisted and on occasion has been associated with adverse outcomes, particularly when the drug is taken under suboptimal conditions. LSD's potential to cause psychological disturbance (bad trips) has been long understood, and has rarely been associated with accidental deaths and suicide. From a physiological perspective, however, LSD is known to be non-toxic and medically safe when taken at standard dosages (50-200µg). The scientific literature, along with recent media reports, have unfortunately implicated "LSD toxicity" in five cases of sudden death. On close examination, however, two of these fatalities were associated with ingestion of massive overdoses, two were evidently in individuals with psychological agitation after taking standard doses of LSD who were then placed in maximal physical restraint positions (hogtied) by police, following which they suffered fatal cardiovascular collapse, and one case of extreme hyperthermia leading to death that was likely caused by a drug substituted for LSD with strong effects on central nervous system temperature regulation (e.g. 25i-NBOMe). Given the renewed interest in the therapeutic potential of LSD and other psychedelic drugs, it is important that an accurate understanding be established of the true causes of such fatalities that had been erroneously attributed to LSD toxicity, including massive overdoses, excessive physical restraints, and psychoactive drugs other than LSD.

Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA.

4-phosphorloxy-N,N-dimethyltryptamine (psilocybin) and methylenedioxymethamfetamine (MDMA), best known for their illegal use as psychedelic drugs, are showing promise as therapeutics in a resurgence of clinical research during the past 10 years. Psilocybin is being tested for alcoholism, smoking cessation, and in patients with advanced cancer with anxiety. MDMA is showing encouraging results as a treatment for refractory post-traumatic stress disorder, social anxiety in autistic adults, and anxiety associated with a life-threatening illness. Both drugs are studied as adjuncts or catalysts to psychotherapy, rather than as stand-alone drug treatments. This model of drug-assisted psychotherapy is a possible alternative to existing pharmacological and psychological treatments in psychiatry. Further research is needed to fully assess the potential of these compounds in the management of these common disorders that are difficult to treat with existing methods.

MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults.

The first study of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of social anxiety in autistic adults commenced in the spring of 2014. The search for psychotherapeutic options for autistic individuals is imperative considering the lack of effective conventional treatments for mental health diagnoses that are common in this population. Serious Adverse Events (SAEs) involving the administration of MDMA in clinical trials have been rare and non-life threatening. To date, MDMA has been administered to over 1133 individuals for research purposes without the occurrence of unexpected drug-related SAEs that require expedited reporting per FDA regulations. Now that safety parameters for limited use of MDMA in clinical settings have been established, a case can be made to further develop MDMA-assisted therapeutic interventions that could support autistic adults in increasing social adaptability among the typically developing population. As in the case with classic hallucinogens and other psychedelic drugs, MDMA catalyzes shifts toward openness and introspection that do not require ongoing administration to achieve lasting benefits. This infrequent dosing mitigates adverse event frequency and improves the risk/benefit ratio of MDMA, which may provide a significant advantage over medications that require daily dosing. Consequently, clinicians could employ new treatment models for social anxiety or similar types of distress administering MDMA on one to several occasions within the context of a supportive and integrative psychotherapy protocol.