Are psychedelic medicines the reset for chronic pain? Preliminary findings and research needs.

Chronic pain is a leading cause of disability, reduced productivity, healthcare seeking behavior, and a contributor to opioid overdose in the United States. For many people, pain can be satisfactorily managed by existing medicines and comprehensive psychosocial treatments. For others, available treatments are either ineffective or not acceptable, due to side effects and concerns about risks. Preliminary evidence suggests that some psychedelics may be effective for certain types of pain and/or improved quality of life with increased functionality and reduced disability and distress in people whose pain may never be completely relieved. Efficacy in these quality-of-life related outcomes would be consistent with the 'reset in thinking' about chronic pain management being increasingly called for as a more realistic goal for some people as compared to complete elimination of pain. This commentary summarizes the rationale for conducting more basic research and clinical trials to further explore the potential for psychedelics in chronic pain management. Additionally, if shown to be effective, to then determine whether the effects of psychedelics are primarily due to direct antinociceptive or anti-inflammatory mechanisms, or via increased tolerability, acceptance, and sense of spirituality, that appear to at least partially mediate the therapeutic effects of psychedelics observed in psychiatric disorders such as major depression. This commentary represents a collaboration of clinical and more basic scientists examining these issues and developing recommendations for research ranging from neuropharmacology to the biopsychosocial treatment factors that appear to be as important in pain management as in depression and other disorders in which psychedelic medicines are under development. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".

National Institutes of Health psilocybin research speaker series: State of the science, regulatory and policy landscape, research gaps, and opportunities.

The U.S. National Institutes of Health (NIH) convened a seminal first ever psychedelic drug substance-focused speaker series, from April 22 to June 10, 2021, titled the "NIH Psilocybin Research Speaker Series." This speaker series provided evidence-based scientific information to the public and the scientific community. Its aims were to assess the current state of the science, the regulatory and policy landscape, as well as to identify gaps in knowledge and understanding, ultimately serving to define future research needs. The highlights of the lectures and discussion from 26 national and international distinguished experts served as the basis for this Special Issue of Neuropharmacology. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".

Psychedelic drug abuse potential assessment research for new drug applications and Controlled Substances Act scheduling.

New medicines containing classic hallucinogenic and entactogenic psychedelic substance are under development for various psychiatric and neurological disorders. Many of these, including psilocybin, lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA) are Schedule I controlled substances of the United States Controlled Substances Act (US CSA), and similarly controlled globally. The implications of the CSA for research and medicines development, the path to approval of medicines, and their subsequent removal from Schedule I in the US are discussed. This entire process occurs within the framework of the CSA in the US and its counterparts internationally in accordance with international drug control treaties. Abuse potential related research in the US informs the eight factors of the CSA which provide the basis for rescheduling actions that must occur upon approval of a drug that contains a Schedule I substance. Abuse-related research also informs drug product labeling and the risk evaluation and mitigation strategies (REMS) will likely be required for approved medicines. Human abuse potential studies typically employed in CNS drug development may be problematic for substances with strong hallucinogenic effects such as psilocybin, and alternative strategies are discussed. Implications for research, medicinal development, and controlled substance scheduling are presented in the context of the US CSA and FDA requirements with implications for global regulation. We also discuss how abuse-related research can contribute to understanding mechanisms of action and therapeutic effects as well as the totality of the effects of the drugs on the brain, behavior, mood, and the constructs of spirituality and consciousness.

The National Cancer Institute's Conference on Acupuncture for Symptom Management in Oncology: State of the Science, Evidence, and Research Gaps.

The Division of Cancer Treatment and Diagnosis, Office of Cancer Complementary and Alternative Medicine, at the National Cancer Institute (NCI) held a symposium on "Acupuncture for Cancer Symptom Management" on June 16 and 17, 2016. Invited speakers included 19 scientists and scholars with expertise in acupuncture and cancer research from the United States, Europe, and China. The conference reviewed the NCI's grant funding on acupuncture, analyzed the needs of cancer patients, reviewed safety issues, and assessed both the current scientific evidence and research gaps of acupuncture in oncology care. Researchers and stakeholders presented and discussed basic mechanisms of acupuncture; clinical evidence for specific symptoms; and methodological challenges such as placebo effects, novel biostatistical methods, patient-reported outcomes, and comparative effectiveness research. This paper, resulting from the conference, summarizes both the current state of the science and clinical evidence of oncology acupuncture, identifies key scientific gaps, and makes recommendations for future research to increase understanding of both the mechanisms and effects of acupuncture for cancer symptom management.

The Role of Grape Seed Extract in the Treatment of Chemo/Radiotherapy Induced Toxicity: A Systematic Review of Preclinical Studies.

Grapes are one of the most consumed fruits in the world and are rich in polyphenols. Grape seed proanthocyanidins (GSP) have demonstrated chemopreventive and/or chemotherapeutic effects in various cancer cell cultures and animal models. The clinical efficacy of chemotherapy is often limited by its adverse effects. Several studies show that reactive oxygen species mediate the cardiotoxicity and neurotoxicity induced by various cancer chemotherapeutic agents. This implies that concomitant administration of antioxidants may prevent these adverse effects. The review was carried out in accordance with the PRISMA guidelines. An electronic search strategy in Medline and Embase databases was conducted. Of the 41 studies reviewed, 27 studied GSP while the remainder (14) studied grape seed or skin extracts (GSE). All the studies were published in English, except 2 in Chinese. A significant percentage (34%) of the studies we reviewed assessed the effect of GSE or GSP on cardiotoxicity induced by chemotherapy. Doxorubicin was the most common chemotherapeutic drug studied followed by cisplatin. Research studies that assessed the effect of GSE or GSP on radiation treatment accounted for 22% of the articles reviewed. GSE/GSP ameliorates some of the cytotoxic effects on normal cells/tissues induced by chemo/radiotherapy.