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.

Ethical Concerns about Psilocybin Intellectual Property.

Since a 1957 exposé in Life Magazine, chemical compounds derived from Psilocybe mushrooms have been the focus of dozens of attempted and successful patents, most recently to treat depression. Regrettably, the Mazatec indigenous communities who stewarded these traditional medicines for millenia are not party to any of these patents, despite a number of international treaties asserting indigenous rights to their intangible cultural heritage.

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil

Objective: To conduct Brazil's first clinical trial employing 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder (PTSD), given its high prevalence resulting from epidemic violence. Methods: Of 60 volunteers, four matched the inclusion & exclusion criteria. Three patients with PTSD secondary to sexual abuse (diagnosed by the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale for DSMV-4 [CAPS 4]) completed enrollment and treatment, following a standardized Multidisciplinary Association for Psychedelic Studies protocol consisting of 15 weekly therapy sessions: three with orally administered MDMA with concurrent psychotherapy and music, spaced approximately 1 month apart. CAPS-4 scores two months after the final MDMA session were the primary outcome. Results: No serious adverse events occurred. The most frequent adverse events were somatic pains and anguish. CAPS-4 reductions were always greater than 25 points. The final scores were 61, 27, and 8, down from baseline scores of 90, 78, and 72, respectively. All reductions were greater than 30%, which is indicative of clinically significant improvement. Secondary outcomes included lower Beck Depressive Inventory scores and higher Post-Traumatic Growth Inventory and Global Assessment of Functioning scores. Conclusions: Considering the current limitations in safe and efficacious treatments for PTSD and recent studies abroad with larger patient samples, MDMA-assisted psychotherapy could become a viable treatment in Brazil. Clinical trial registration: RBR-6sq4c9

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil.

OBJECTIVE: To conduct Brazil's first clinical trial employing 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder (PTSD), given its high prevalence resulting from epidemic violence. METHODS: Of 60 volunteers, four matched the inclusion & exclusion criteria. Three patients with PTSD secondary to sexual abuse (diagnosed by the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale for DSMV-4 [CAPS 4]) completed enrollment and treatment, following a standardized Multidisciplinary Association for Psychedelic Studies protocol consisting of 15 weekly therapy sessions: three with orally administered MDMA with concurrent psychotherapy and music, spaced approximately 1 month apart. CAPS-4 scores two months after the final MDMA session were the primary outcome. RESULTS: No serious adverse events occurred. The most frequent adverse events were somatic pains and anguish. CAPS-4 reductions were always greater than 25 points. The final scores were 61, 27, and 8, down from baseline scores of 90, 78, and 72, respectively. All reductions were greater than 30%, which is indicative of clinically significant improvement. Secondary outcomes included lower Beck Depressive Inventory scores and higher Post-Traumatic Growth Inventory and Global Assessment of Functioning scores. CONCLUSIONS: Considering the current limitations in safe and efficacious treatments for PTSD and recent studies abroad with larger patient samples, MDMA-assisted psychotherapy could become a viable treatment in Brazil. CLINICAL TRIAL REGISTRATION: RBR-6sq4c9.

Neural correlates of the LSD experience revealed by multimodal neuroimaging.

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.

Ayahuasca and cancer treatment.

OBJECTIVES: Comprehensively review the evidence regarding the use of ayahuasca, an Amerindian medicine traditionally used to treat many different illnesses and diseases, to treat some types of cancer. METHODS: An in-depth review of the literature was conducted using PubMed, books, institutional magazines, conferences and online texts in nonprofessional sources regarding the biomedical knowledge about ayahuasca in general with a specific focus in its possible relations to the treatment of cancer. RESULTS: At least nine case reports regarding the use of ayahuasca in the treatment of prostate, brain, ovarian, uterine, stomach, breast, and colon cancers were found. Several of these were considered improvements, one case was considered worse, and one case was rated as difficult to evaluate. A theoretical model is presented which explains these effects at the cellular, molecular, and psychosocial levels. Particular attention is given to ayahuasca's pharmacological effects through the activity of N,N-dimethyltryptamine at intracellular sigma-1 receptors. The effects of other components of ayahuasca, such as harmine, tetrahydroharmine, and harmaline, are also considered. CONCLUSION: The proposed model, based on the molecular and cellular biology of ayahuasca's known active components and the available clinical reports, suggests that these accounts may have consistent biological underpinnings. Further study of ayahuasca's possible antitumor effects is important because cancer patients continue to seek out this traditional medicine. Consequently, based on the social and anthropological observations of the use of this brew, suggestions are provided for further research into the safety and efficacy of ayahuasca as a possible medicinal aid in the treatment of cancer.

Fear conditioning performance and NMDA receptor subtypes: NR2A differential expression in the striatum.

While considerable evidence implicates NMDA receptors in the hippocampus in contextual fear conditioning, the role of other brain regions is less well understood. To further investigate this issue, rats were subjected to a contextual fear conditioning task and then classified as high or low responders according to performance. Density of NMDA receptors was evaluated using [3H]MK-801 autoradiography in 52 brain areas and expression of NR2A and NR2B subunits was studied with in situ hybridization in the same brains. Results revealed no differences between high- and low-performance rats in NMDA receptor binding in any of the brain areas studied. Similarly, NR2B subunit expression was also not different between groups. However, NR2A expression was significantly higher in the caudate-putamen of low-performance rats. These results suggest that NMDA receptors in the caudate-putamen may also be involved in contextual fear conditioning performance.