Life at the Johns Hopkins School of Medicine
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A priest, a minister and a rabbi walk into Johns Hopkins Bayview Medical Center to ingest psilocybin, the active ingredient in hallucinogenic mushrooms. Although this probably sounds like the beginning of a great joke, new advancements in the field of psychedelic medicine are no laughing matter.
After nearly 50 years of prohibition, academic studies and clinical trials have recently begun to examine illegal and psychedelic drugs as treatment tools for a variety of physiological and psychological conditions. Of these, marijuana has been at the forefront, based on growing evidence of its beneficial applications as a treatment for diverse pathologies, including glaucoma, seizures and chronic pain. This has led to an increased acceptance of the plant in the medical pharmacopeia, and indeed, its legalization for medical use has increased from four to 25 states since 2000. Similarly, ketamine, a dissociative anesthetic conventionally used in veterinary medicine, has shown remarkable efficacy in recent trials for treating depression. The psychoactive compound MDMA, or Ecstasy, is being utilized in conjunction with psychotherapy to treat patients with post-traumatic stress disorder, with remarkable results. The success of this combination has been so dramatic that the Food and Drug Administration recently fast-tracked the MDMA-assisted psychotherapy phase III clinical trials that are already underway in hopes of determining an acceptable medical use of the drug by 2021.
This recent resurgence in psychedelic studies is exciting but not necessarily surprising for two researchers at Johns Hopkins Bayview. Roland Griffiths and Matthew Johnson have been examining the powerful effects of psilocybin in a variety of contexts for over a decade, and both are optimistic about its future applications as an accepted pharmaceutical. In collaboration with a small group of researchers from several universities around the world, Griffiths and Johnson have demonstrated that psilocybin-assisted psychotherapy can help induce and maintain behavioral changes, such as quitting nicotine or cocaine, as well as psychological changes, including reduction in depression symptoms and end-of-life anxiety associated with terminal cancers. In both cases, preliminary trials have demonstrated efficacy rates over 80 percent, which were maintained for at least one year.
The first psilocybin study Griffiths completed in 2006 examined the concept of the “mystical experience” in volunteers. The majority of study participants experienced significant feelings of “unity ... an interconnectedness of all things ... sacredness of life,” and over 60 percent reported it as the most meaningful experience of their lives. In further studies, Griffiths showed a consistent correlation between individuals’ self-reporting of this mystical experience and the success of their treatment. Strikingly, those with the most success quitting smoking or resolving symptoms of depression all reported high levels of this mystical aspect. To better understand this phenomena, Griffiths and Johnson are now recruiting religious leaders to engage in a study where they will use psilocybin in a therapeutic setting and report exclusively on its effects to their own deeply held beliefs. Griffiths believes the benefit will be twofold: These participants will be better able to communicate the mystical experience to researchers, and may also enrich their own congregation and vocation in a new and powerful way.
Psychedelic researchers are quick to distinguish that these positive effects in clinical settings do not mean the drugs are suddenly safe to use by anyone, anytime. Instead, they advocate strongly for controlled consumption, with a well-trained clinician guiding the patient through the experience to highlight positive growth and outcomes.
Originally made illegal during the Nixon administration, psychedelics have been placed on the Schedule I list for having “no medicinal value” for nearly 50 years. But as a remarkable body of evidence to the contrary is collected by researchers like Griffiths and Johnson, the country must begin to more seriously discuss how to best incorporate these substances into the medical field so their positive effects may reach the patients who need them.
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Precision medicine, or personalized medicine, is a growing field that uses big data to treat the individual patient. It uses tools such as DNA sequencing and bioinformatics to ask, “What are the individual characteristics of my patient?” — for example, in her genetic makeup, environment or in the mutation profile of her tumor — and then examines whether this information can be incorporated into medical decision-making. With President Obama’s 2015 Precision Medicine Initiative, the United States government has launched a multimillion-dollar investment in supporting precision medicine.
One of the leaders in this field is Dan Roden, who currently serves as the vice president for personalized medicine at Vanderbilt University. On Oct. 5, Roden gave the 2016 Sir Henry Hallett Dale Memorial Lecture at The Johns Hopkins University in a talk titled “Engineering a Healthcare System for Discovery and Implementation in Precision Medicine.”
Tailoring disease prognoses or choice of drug treatment to the individual patient is not a new concept, and Roden began by giving several examples of how patients’ genetic makeup is already being used to predict their risk of drug side effects. One such drug is procainamide, which is prescribed to treat cardiac arrhythmias. Liver enzymes modify the chemical structure of procainamide in a process called acetylation. People who have a genetic deficiency in these enzymes are called slow acetylators, whereas those with a gene that instead confers strong enzyme activity are called rapid acetylators. Since the 1970s, it has been known that slow acetylators who use procainamide have an increased risk of developing a lupuslike side effect called drug-induced lupus erythematosus. Although procainamide is not a commonly prescribed medication, knowledge of acetylation status could help doctors prescribe the right drug dose to maximize its effectiveness while minimizing the risk of side effects.
How can we broaden our efforts to find gene variants that impact disease prognosis, response to therapy or risk of adverse side effects? By combining large-scale molecular profiling and data collection with bioinformatics, Roden described ongoing projects in precision medicine aimed at discovering new associations. For example, during the check-in process at Vanderbilt outpatient clinics, patients are now given a consent form for a program called BioVU. If they choose to participate, their DNA will be extracted from any blood left over from routine blood tests that would have otherwise been discarded. The DNA is then stored in a de-identified database that can be accessed by researchers. In a related project, called eMERGE, DNA repositories like BioVU are linked with curated clinical data from the patients’ electronic health records, providing a platform for bioinformaticians to mine through the data and uncover new links among specific gene variants, diseases and therapy outcomes.
As an M.D.-Ph.D. student interested in translational medicine, I was particularly curious about tools that could guide clinicians to make better-informed medical decisions based on research findings in precision medicine. One tool is to build guidelines directly into the electronic health record, as Vanderbilt has already done for the drug clopidogrel. In 2010, the FDA added a warning to clopidogrel, a medicine used to prevent blood clots, stating that individual genetic variation alters the efficacy of the drug. Patients who have decreased activity of another liver enzyme due to variants in the CYP2C19 gene are “poor metabolizers” who cannot effectively transform clopidogrel into its active form. Alternative drugs are recommended for patients who are poor metabolizers.
By actively displaying this drug-genome interaction in the patient’s electronic health record, Vanderbilt saw dramatic changes in clinical decision-making related to clopidogrel use. Twelve months into the project, fewer poor metabolizer patients remained on clopidogrel, compared to extensive metabolizer patients (42 percent versus 92 percent), whereas intermediate metabolizers were right in the middle, at 67 percent. Unlike procainamide, clopidogrel is a widely prescribed drug that is used daily by millions of Americans.
The combination of precision medicine and the electronic health record promises to open exciting new possibilities not only to better understand the relationship between genetics and disease, but also to better treat the patient as an individual.
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