Monthly Archives: September 2022

RESEARCH UPDATE

Lysergic acid diethylamide (LSD) and psilocybin are serotonergic psychedelics that are candidates for the treatment of psychiatric disorders.1-4 Both agents stimulate serotonin 5-HT2A receptors; LSD also acts at dopamine D13-3 receptors, and the active metabolic of psilocybin (psilocin) inhibits the serotonin transporter.5 The similarities, acute effects, and dose equivalence of these agents in humans remains unclear.

The Current Study

Holze and colleagues6 directly compared the acute subjective, autonomic, and endocrine effects of LSD and psilocybin at 2 doses and placebo within the same participants. The acute subjective effects of these agents were assessed with validated psychometric instruments, and pharmacokinetic data were obtained over 24 hours. The investigators performed a double-blind, placebo-controlled crossover study with 5 experimental test sessions (placebo, LSD 100 g, LSD 200 g, psilocybin 15 mg, psilocybin 30 mg), with a washout period of at least 10 days between sessions.

The authors recruited 28 healthy participants; their mean age was 35 years and 50% were male. Exclusion criteria were: age less than than 25 years or greater than 65 years, pregnancy, family history of major psychiatric disorders in first-degree relatives, current psychotropic medication use, acute or chronic physical illness, tobacco smoking of more than 10 cigarettes/day, lifetime illicit drug use exceeding 10 times (except use of tetrahydrocannabinol [THC], the principal psychoactive cannabinoid of cannabis), or illicit drug use in the past 2 months or during the study period. In terms of previous drug use, 11 participants had previously used LSD and 6 had previously used psilocybin; 13 had previously used a stimulant; and 10 participants had no history of noncannabis illicit drug use. LSD was administered as an oral solution and psilocybin as an oral capsule. A double-dummy method was used such that participants received 6 capsules and 2 solutions at each test session.

Each test session lasted 25 hours and was conducted in a calm hospital room. Abstinence from illicit drugs was verified with a urine drug screen. Outcomes were repeatedly assessed for 24 hours. Standardized meals were served. An investigator was present in the room during the acute effect phase and remained in a room next to the participant for up to 24 hours. Subjective effects were assessed repeatedly using visual analogue scales (VAS), the Adjective Mood Rating Scale (AMRS), the 5 Dimensions of Altered States of Consciousness scale (5D-ASC), and the Mystical Effects Questionnaire(MEQ). Effect durations were assessed using the classic pharmacokinetic-pharmacodynamic link module. Blood pressure, heart rate, and temperature were repeatedly measured. Adverse effects were assessed 1 hour before and 12 and 24 hours after drug administration. Plasma LSD and psilocybin concentrations, and cortisol, prolactin, oxytocin, and brain-derived neurotrophic factor (BDNF) measurements were also obtained at multiple time points. Pharmacokinetic parameters were estimated using noncompartmental methods. Peak drug effects (minimum, maximum, or change from baseline) were determined for repeated measures, then analyzed using repeated-measures analysis of variance.

Both doses of LSD and the 30-mg psilocybin dose produced comparable subjective effects, based on VAS and 5D-ASC outcomes. There was significantly greater ego dissolution and a trend toward greater anxiety with 200 g versus 100 g LSD. Psilocybin 15 mg had significantly lower effects than psilocybin 30 mg and both LSD doses, based on VAS and 5D-ASC outcomes. Both LSD doses had significantly increased emotional excitation on the AMRS compared with psilocybin. There were no differences in subjective effects of LSD or psilocybin based on sex.

Both LSD and psilocybin significantly increased systolic and diastolic blood pressure, temperature, and pupil diameter compared with placebo. Psilocybin 30 mg produced significantly greater increases in blood pressure and temperature compared with psilocybin 15 mg and both doses of LSD. By contrast, both LSD doses produced a greater increase in pulse compared with both psilocybin doses and placebo. Psilocybin produced greater impairments in pupil contraction compared with LSD. Both LSD and psilocybin increased the total acute (0-12 hours) adverse effect score compared with placebo. Subacute (12-24 hours) adverse effect scores were significantly greater with LSD 200 g LSD and psilocybin 30 mg compared with placebo. The most common adverse effects were headaches. Five participants had 9 flashback episodes within 72 hours. No severe adverse events were observed.

Both LSD doses had significantly longer effect durations (10-11 versus 6-7 hours) and earlier onset of effects (0.4-0.6 versus 0.8 hours) compared with both psilocybin doses. The elimination half-life values were about 4 hours for LSD and 2.5 hours for psilocybin. Both LSD and psilocybin significantly increased plasma cortisol, prolactin, and oxytocin levels, but neither affected BDNF levels. Both LSD and psilocybin showed linear pharmacokinetics, which were not influenced by body weight.

In terms of blinding, no clear distinction between LSD and psilocybin could be made after the session or at study end point. Participants correctly identified the psychedelic and dose in about 60% of sessions, compared with 96% for placebo.

Study Conclusions

The authors investigated and directly compared the acute effects of LSD and psilocybin in healthy participants in a well-blinded study. They concluded that psilocybin 15 mg exerted clearly weaker subjective effects, and both agents had dose-dependent effect durations (significantly longer for LSD), stimulant autonomic effects, and increased endocrine parameters. Body weight had no influence on blood concentrations. The investigators noted the data further supported the notion that states of consciousness alteration induced by LSD and psilocybin are more likely dose-dependent rather than substance-dependent. In addition, they concluded the differences in the pharmacological profiles of LSD and psilocybin do not relevantly influence subjectively experienced effects of both psychedelics.

Study strengths included the within-subjects design and the use of well-characterized, fixed dosing. The primary study limitations were the use of a highly controlled setting and the participation of healthy participants only.

The Bottom Line

This study supports dose finding for research and psychedelic-assisted therapy. Psilocybin 20 mg is likely equivalent to LSD 100 g. There was no evidence for qualitative differences in altered states of consciousness, except for a shorter duration of action for psilocybin.

Dr Miller is a professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric Times. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.

References

1. Carhart-Harris R, Giribaldi B, Watts R, et al. Trial of psilocybin versus escitalopram for depression. N Engl J Med. 2021;384(15):1402-1411.

2. Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol. 2016;30(12):1181-1197.

3. Davis AK, Barrett FS, May DG, et al. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2021;78(5):481-489.

4. Gasser P, Kirchner K, Passie T. LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects. J Psychopharmacol. 2015;29(1):57-68.

5. Rickli A, Moning OD, Hoener MC, Liechti ME. Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. Eur Neuropsychopharmacol. 2016;26(8):1327-1337.

6. Holze F, Ley L, Muller F, et al. Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects. Neuropsychopharmacology. 2022;47(6):1180-1187.

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Effects of LSD and Psilocybin in Healthy Participants - Psychiatric Times

A 49-year-old woman with advanced metastatic breast cancer has successfully halted the spread of the disease with chemotherapy alongside cannabis oil and magic mushrooms, according to a new case report. After halting her conventional cancer treatment, the patient remained disease-free for 18 months while using only cannabis and psilocybin, but experienced a recurrence when she stopped self-medicating with these psychoactive drugs.

Sensational as this sounds, its important not to get carried away by a single case study or to jump to conclusions about whether or not weed and psychedelics were responsible for the patients remarkable recovery. Being an observational study, the report does not provide any biomedical analysis of the womans disease progression or treatment protocol.

The patient was first diagnosed with stage IV breast cancer in August 2018 and soon learned that the disease had spread to her bones, liver, and lymph nodes. She was immediately prescribed a course of chemotherapy and took the personal decision to begin self-treating with cannabis oil. From November of that year, the patient also underwent her first session of psychedelic therapy, ingesting a large dose of magic mushrooms under the supervision of a trained therapist.

Incredibly, scans conducted in January 2019 revealed that the cancer had completely vanished, with no evidence of residual or recurrent disease.

This highlights in the first phase of treatment the possibility of the therapeutic adjunctive effect of both psychedelics and cannabinoids in treating metastatic breast cancer, say the study authors.

Chemotherapy was subsequently stopped while the patient continued to take daily doses of cannabis oil plus magic mushroom microdoses. She also went a further three sessions of high-dose psychedelic therapy over the next two years.

Follow-up scans in September 2019 indicated that the cancer had not returned, at which point the patient reduced her cannabis intake to 56 percent of the initial dose while also temporarily halting the shrooms. However, further tests conducted in June 2020 revealed a recurrence of the disease.

This brings up the possibility that withdrawal of the cannabinoid and psychedelic therapies may have contributed to the return of the cancer, write the study authors.

Having received this news, the patient reintroduced psychedelics to her treatment regimen and boosted her cannabinoid ingestion. By October 2021, a stabilization of the illness was observed, although no details are provided as to the severity of the cancer at this stage.

Though the researchers are unable to explain how or indeed if this self-medication approach successfully arrested the patients cancer, they do point to pre-clinical studies hinting at the tumor-busting potential of both cannabis and psychedelics. For instance, research has shown that compounds in weed and magic mushrooms may inhibit a protein called Hypoxia-Inducible Factor (HIF)-1, which facilitates the development of blood vessels within tumors.

However, this has yet to be demonstrated in human cancer patients and there is no hard evidence that either cannabis or psychedelics have any direct impact on tumor development.

Nonetheless, the study authors conclude that the overall picture of the case presents the strong possibility that cannabinoids and psychedelics have played an important modulatory or additive role to standardized treatment, which warrants further exploration.

The study was published in the journal Drug Science.

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Cannabis And Psilocybin May Have Helped This Woman's Breast Cancer Treatment - IFLScience

The formal lawns and topiary of the garden in which Amanda Feilding, Countess of Wemyss and March, is sitting embody a perfect English orderliness; beyond its edge lies a wilderness of Anglo-Saxon moats, sun-dappled woodland and magical stepping-stone trails. This promise of untamed hinterlands puts the grounds of Beckley Park in perfect sync with their mistress. Lady Wemyss is the queen of psychedelics.

Psychedelics have a history which is probably longer than that of civilisation. They have powerful effects on the brain and their lore is rich in anecdotes about effects on mental health, some for better and some for worse. As pharmaceutical companies tried to find new approaches to the brain, the potential of psychedelics might have seemed an obvious road to go down. But law and stigma blocked it. Until five years ago corporate investment in psychedelics as medicines was more or less unthinkable.

Work by Lady Wemysss Beckley Foundation, the Multidisciplinary Association for Psychedelic Studies (maps) in San Jose, California, and other such groups have helped to change that. So has the broadening acceptance of marijuana as a medicine and the softening or repeal of laws limiting its use. A change in the attitude of regulators and researchers towards running proper trials of the drugs has also contributed. Applying modern scientific techniques to the question of how psychedelics and other drugs affect the brain and mind is now seen as opening up possibilities for insight, treatment and profit.

The pioneer in this re-evaluation has been ketamine, an anaesthetic that is also used recreationally. About 20 years ago anecdotal evidence that the drug had an effect on depression led to academic trials; the work piqued the interest of j&j, a big drug company. The ketamine sold generically is a mixture of two compounds with the same chemical formula; j&j won a patent on a nasal spray called Spravato which contained just one of those compounds, s-ketamine. Americas Food and Drug Administration (fda) approved it as a treatment for major depression in 2019.

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Barefoot in the cross-head

Spravato demonstrated the potential of innovation based on recreational drugs: it was the first drug for depression based on a novel biological mechanism to have been approved in 30 years. But it has not been a big commercial success. It is expensive and has to be taken under medical supervision, which adds to costs and faff.

Despite that, all manner of drugs that were mooted as being psychiatrically beneficial in the 1960s are finally being put through their paces in rigorous clinical trials under the eyes of strict regulators like the fda. Dimethyltryptamine, ibogaine, lsd, mdma and psilocybin are being tried. These drugs are targeting the treatment of addiction, anxiety, depression, eating disorders and post-traumatic stress disorder (ptsd).

Within 24 hours of a single dose of psilocybin there was a 10% increase in the number of neuronal connections and some connections were stronger

The non-profit group maps is looking at mdma-assisted therapy for ptsd. mdma, widely known as ecstasy, is a small, amphetamine-like molecule prized for creating feelings of empathy. The maps trial put participants through three preparatory sessions, three sessions in which either mdma or a placebo was administered and nine post-treatment therapy sessions. At the end, 67% of participants in the mdma group no longer met the diagnostic criteria for ptsd, compared with 32% in the placebo group.

Psilocybin is a focus for compass Pathways, a London-based startup. Last year it published the results of a trial comparing different doses of psilocybin, all paired with therapy, in cases of treatment-resistant depression (trd). Three weeks after treatment 29% of those who got the highest dose were in remission.

Given what the tr in trd stands for, a response rate of almost 30% was exciting to scientists. But it was a disappointment to many who had been listening only to the media hype about the potential of psychedelics. The remission seen by fewer than one in three did not always last; only one in four were still in remission three months on. And three of the patients in the high-dose group displayed suicidal behaviour, compared with none in the other cohorts. Suicidality is common in trd and in trials of anti-depressants, but it is nonetheless a cause for concern.

One of the two underlying capabilities of psychedelics that interests researchers is that they seem to be able rapidly to induce neural plasticityphysical changes in the growth of neurons and of the connections between them. A recent study by scientists at the Yale University School of Medicine showed that, within 24 hours of a single dose of psilocybin, neurons in the prefrontal cortex of a mouse brain changed; their dendritesthe bits which receive inputs from their neighboursgrew longer and denser. There was a 10% increase in the number of neuronal connections and evidence that some of those connections were stronger.

Think of the neurons as close-packed trees flourishing in the lush gardens of the prefrontal cortex, which organises thoughts and actions. Dendrites are their tangled branches. A healthy brain has a rich canopy. Withered branches can lead to losses in connectivity and less communication between the context and areas associated with motivation and reward.

In the study, the connections between neurons in the mices brains became both more numerous and stronger, suggesting connectivity was improved. Not all the changes lasted; but a month later some were still visible. And they were correlated with changes in the animals stress-related behaviour.

The drugs trigger this sort of change in the neurons by activating various combinations of a specific set of receptor proteins which includes three types of serotonin receptor (5-ht1b, 5-ht2a and 5-ht2b) and nmda, a glutamate receptor. Different drugs favour different receptors (see diagram) which is why they have different effects. mdma, which produces psychedelic-like effects but without hallucinations, works on the 5-ht2 receptors, inducing a rapid release of serotonin and dopamine. Ketamine and ibogaine, which is extracted from an African shrub, both work on nmda as well as other receptorsincluding, in the case of ketamine, opioid receptors. The biochemistry of this is also linked to anatomy. Activation of 5-ht2ain which the visual cortex is comparatively richseems to be necessary (although not sufficient on its own) to generate hallucinations.

If plasticity is one interesting aspect of psychedelics, the other is that by firing up receptors they also disrupt activity within the brains neural networks. Srinivas Rao, the chief scientific officer of atai Life Sciences, a German company that specialises in psychiatric drugs, says the psychedelics and their kin are loosening connections in the brain and then altering network functions. Atai is pursuing ketamine for trd and ibogaine for opioid addiction.

Dr Rao warns that psychedelics are not going to be cures for most people with chronic conditions like depression. The loosening of connections in a network-disrupting trip might shift some of them out of a rut; it will not stop them returning to it. But many think the drugs open the door for talking therapies to work better and for patients themselves to initiate new approaches to life. A few patients will be lucky enough to have durable responses. Guy Goodwin of compass Pathways sees psychedelic treatment as a way for some patients to achieve a step change. It may be for a minority, he admits. How we increase that minority is a question we are going to have to work on in the future.

There are other factors which could limit the uptake of these medicines. Like Spravato they will probably be approved for use only in certified health-care settings and with strict protocols; a patient given a dose of psilocybin, or mdma, requires many hours of supervision. That makes these drugs very unlikely to be the first line of therapy offered to people who roll up at their doctors office with depression or anxiety. They are also likely to be approved for use only in the context of psychotherapy.

Such requirements may mean that more people seek the benefits more cheaply. The approval of Spravato coincided with an uptick in the use of generic ketamine, given by intravenous infusion, in clinics across America and Europe. And the drugs in question are all, more or less by definition, available informally.

Whos for a short, unstrange trip?

One alternative would be to develop second-generation drugs based on the same principles but more easily administered. Delix Therapeutics, based in Boston, Massachusetts, is heading full tilt to the creation of psychedelic substances with the hallucinatory effects eliminated, which would mean they could be used by patients without supervision. Dave Olsen, chief innovation officer at Delix, says the drugs work because they encourage neuroplasticity; if that is the case, then the trippiness may not be necessary. He points to studies showing that dental patients anaesthetised with ketamine wake up with an enhanced mood; having some kind of conscious experience is not integral to the drugs effects.

There will be potential patients who hope he is right. Some proponents of psychedelics think the mystical experience is integral to the clinical outcome, revealing insights into the psyche that are impossible to obtain any other way. This means they find it hard to bend their minds around the idea that some of the mentally unwell do not want to change their consciousness. They just want to get better. Rory, a hairdresser from Lancashire, had suffered from depression all his life; he had tried everything and was keen to find something that worked. Yet his first experience with a ketamine infusion was so horrendous he did not want to come back.

Delix, for its part, is not saying that the world does not need hallucinogens to treat mental-health disorders, nor that the network effects they offer are not useful. It is just saying that drugs that do only part of what psychedelics do could be useful in and of themselves. Dr Rao says, being empiric I view the hallucinations as a manifestation of network disruption.

Psychedelics are obviously not the be all and end all of new approaches to clinical neuroscience, let alone the one true path to raised consciousness and, as some would have it, humankinds continued evolution. They may well be particularly prone to placebo effects, something it is hard for trials to rule out since people tend to know if they have been given a placebo or sent on a trip. But if high hopes (sorry) seem likely to court disappointment, their study in clinical settings should yield some helpful therapeutic advances and new insights into the way minds sit in brains.

2022 The Economist Newspaper Limited. All rights reserved.

From The Economist, published under licence. The original content can be found on https://www.economist.com/technology-quarterly/2022/09/21/ketamine-psilocybin-and-ecstasy-are-coming-to-the-medicine-cabinet

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Ketamine, psilocybin and ecstasy are coming to the medicine cabinet - Yahoo Finance

Santa Monica, California--(Newsfile Corp. - September 26, 2022) - American Legion Post 123 has officially partnered with Reality Mgmt Technologies (RMT) and its flagship facility Reality Center, located at the heart of Silicon Beach. This partnership will allow the Reality Center team to continue providing patented, drug-free psychedelic experiences to veterans in order to help treat post traumatic stress.

Since January of this year, the RMT team has successfully treated more than 200 veterans suffering from PTS at their new, state-of-the-art sensory wellness center and digital therapeutics lab only steps away from the Santa Monica Pier. These treatments have earned the interest of their local VSO, American Legion Post 123 in Santa Monica,as they became aware of the treatments Reality Center was already offering some of their members.

"Post 123 is committed to integrating our community of veterans with the rapidly growing wellness ecosystem here in Santa Monica," stated Post Commander Bailey Steele. Since partnering, the local American Legion post has been offering free monthly treatments to their members as a way to increase their post 9/11 veteran membership and promote their focus on a new mental health ecosystem.

Reality Center's patented tech and modalities work by combining ancient and modern science. They are able to address a wide array of mental, physical and emotional issues in a one-of-a-kind healing environment. Providing a safe and effective alternative to psychedelics and pharmaceuticals, Reality Center provides a controlled, drug-free experience using frequency technologies to stimulate the nervous system's natural healing mechanisms.

The main treatment veterans experience include Reality Center's most popular offering which involves having each veteran lay on a vibrational platform or liquid mineral bed for 30 minutes while experiencing pulsing lights and synchronized sounds that allow individuals to immediately exit fight or flight and journey deep into their consciousness.

PR Contact: Sharon FoxEmail:sfox@realitymgmt.com

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To view the source version of this press release, please visit https://www.newsfilecorp.com/release/138445

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American Legion and Reality Center Partner to Provide Patented, Drug-Free Psychedelic Experience to Veter - Benzinga

Tahlia Harrison has been bombarded with questions about psychedelics. A practicing therapist, Harrison recently graduated from the bioethics and science policy program at Duke University, where I teach and served as her masters thesis supervisor. Her patients are increasingly interested in experimental regimens that use drugs like LSD, psilocybin, and MDMA to treat post-traumatic stress disorder and other forms of trauma.

Harrisons patients are hardly alone. Since 1970, psychedelics have been considered Schedule I drugs in the U.S., with the feds maintaining that they have no accepted medical use. But in recent years, the government has softened its stance and, accompanied by no small amount of hype, psychedelic-assisted therapies are now being tested in dozens of clinical trials. These studies can present substantial health and safety risks to the patient, and a number of trials have been attached to allegations of sexual abuse. To better understand how these risks are communicated to prospective study participants, earlier this year Harrison set out to collect consent forms used in more than three dozen psychedelic-assisted therapy trials listed on the federally run website clinicaltrials.gov.

To her disappointment, she was able to download consent forms from just five of the trials that met her criteria. And despite directly contacting the organizations running the studies, only one responded to her queries.

Since the long parade of ethics scandals that plagued biomedical research during the 20th century from Nazi doctors experiments, to the Tuskegee Syphilis Study, to a Brooklyn hospital study that injected patients with live cancer cells informed consent has been a hallmark of research on human beings. It enshrines the idea that we cant experiment on people without first informing them of the risks and benefits and, obviously, getting their permission. The consent forms used in clinical trials, as dense and lawyerly as they might be, are meant to answer questions like: What is involved in the study? How long will it take? Will I get paid? What happens if it goes sideways?

But in many cases, few people outside of the researchers, participants, and the institutional review boards charged with approving a study ever see the language used in a trials consent form. Recently, there has been a push toward greater transparency, under the rationale that broadly publicizing the forms researchers use to communicate the risks and benefits of clinical trials will improve accountability, boost public trust in research, and inform the development of future consent forms. But what Harrisons experience, and what my own look at clinicaltrials.gov seem to show, is that the science community isnt pushing nearly hard enough.

A major win for informed consent transparency came in 2018, when federal officials updated the so-called Common Rule a regulation that covers human subjects research funded by 20 U.S. agencies, including the Department of Health and Human Services, under which the National Institutes of Health falls. Effective January 21, 2019, the rule change requires federally funded clinical trials to publish an approved consent form on a public federal website; the form is to be posted after the close of patient recruitment but no later than 60 days after participants last required study visit. Researchers are given an option to upload the form either to clinicaltrials.gov or to a designated folder at the federal website regulations.gov.

Late last year researchers at Brigham and Womens Hospital and the National Library of Medicine found that while the number of posted consent forms is indeed rising, it is hardly keeping pace with the Common Rules requirements. The authors found, for example, that fewer than 18 percent of NIH-funded studies had posted forms.

Late last year researchers at Brigham and Womens Hospital and the National Library of Medicine found that while the number of posted consent forms is indeed rising, it is hardly keeping pace with the Common Rules requirements.

In September, I conducted my own search of clinicaltrials.gov and found that only 283 of the 1,112 federally funded interventional studies listed on the site as having started after January 21, 2019 and finished before January 21, 2022 had uploaded consent forms. Some of the studies had yet to upload any results at all, but even when I limited my search to those that had an idea suggested to me by Geisinger research ethicist Michelle Meyer little more than half had posted consent forms. (I also searched all of the more than 427,000 studies listed at clinicaltrials.gov including past, ongoing, and upcoming studies in the U.S. and elsewhere that arent subject to the Common Rule and found that consent forms had been shared by only 1.3 percent of them.) Meanwhile, the designated folder at regulations.gov,the alternative site where studies may deposit consent forms to satisfy the Common Rule, contained just 44 consent forms posted during the three-year window.

To be fair, some people have sounded alarms about publicly sharing consent forms. In practice, they note, researchers often use the forms less as a way to inform participants and more as a means to mitigate institutional liability. (You cant sue us here at Big Academic Medical Center it was all in the consent form!) At least one group of health care attorneys argued that posting requirements could prompt researchers to write even more stilted, legalistic forms aimed at shielding themselves from lawsuits. The same group also fretted that a rule requiring the public posting of a consent form might confuse participants and the public, because a clinical trial will sometimes use different versions of the form for different participants at different sites, and the consent form might get updated throughout the recruitment process. Who would decide which version to post, and how? Elsewhere, there were concerns that a public posting requirement would stifle innovation, for example, by keeping clinical investigators from exploring novel approaches to consent such as interactive video Q&As.

Public posting of consent form language is a low-risk, low-burden act that could give motivated prospective participants a chance to see what they might be signing up for well ahead of time and gives all stakeholders an opportunity to flag problems.

I was and remain unmoved by these complaints. Publicizing consent forms will make them worse? Wait, what? And sharing them with everyone rather than with just the people you want to participate will necessarily increase liability risks? If so, thats a problem with American jurisprudence and not a justification for opacity. As for the potential confusion over multiple versions of a consent form, in an appropriate consent process prospective participants should always be given the most updated version of the consent form, and an opportunity to ask questions. And one provision of the revised Common Rule mandates that multisite trials use a single institutional review board, which should help standardize consent forms across the different sites. We now have some evidence that this is indeed happening, although some local institutions have been reluctant to cede control.

With respect to video consent and other innovative approaches, the updated Common Rule says nothing about them other than references to electronic format, and its not clear why novel consent processes shouldnt be done transparently: Why not post a link to your consent video on clinicaltrials.gov for all the world to see?

As someone who has served on an institutional review board, read thousands of pages of mind-numbing consent forms, and participated in research as a human subject over the past 15 years, I think that the Common Rule more or less gets it right. Public posting of consent form language is a low-risk, low-burden act that could give motivated prospective participants a chance to see what they might be signing up for well ahead of time and gives all stakeholders an opportunity to flag problems. It could lead to more equitable, safer, better research. Or maybe not. But the only way we can know is by doing the experiment.

For patients like Harrisons, who seek risky but potentially life-saving experimental therapies, the stakes couldnt be higher. Some contend and, for what its worth, I agree that the fervor of the current psychedelic hype cycle is driven more by a messianic push for legitimacy than by an unbiased search for truth. But what if MDMA really works? What if psychedelic-assisted therapy, delivered in a safe environment, can bring relief and healing to people suffering from PTSD and other traumas? Dont we want as many folks as possible considering all of the risks and benefits, the promises and disclaimers? Couldnt controversial psychedelic-assisted therapy studies have benefited from a few more eyes on their consent forms?

We can read millions of scientific papers, court documents, real estate listings, restaurant menus, drug prices, and movie reviews all with just a few keystrokes.

So why not consent forms?

Misha Angrist is associate professor at Duke Universitys Social Science Research Institute and a senior fellow in its Initiative for Science & Society.

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Let's Bring the Informed Consent Process Out of the Shadows - Undark Magazine

Your story Shelter recounts the adventures of an American man on a business trip to Israel who gets caught up in an unexpected drama. What drew you to Cohen as a character?

In the story, Cohen, middle-aged, believes himself to be in stasis, but stumbles unwittingly into a moment of great dynamism. As a younger person, I used to think of middle age the way many coastal people driving across the country think of the Midwest: as a huge, vaguely menacing, but mostly boring expanse where one contemplates how far one has come and how far one still has left to go. I didnt understand what was meant by amidlife crisis,beyond the disappointment of no longer being what I still happily was: fabulously young. For that reason, I mostly avoided middle-aged characters in my writing, preferring the young or the old, whose crises I somehow imagined myself more equipped to fathom. But, now that Ive arrived at middle age myself, I realize that I couldnt have been more mistaken. I guess its always the case that we believe whatever age we are at to be the most interesting. But what a radical, rich, utterly riveting time of life it is! I look around at my friendsadmittedly a lively, searching bunchand Im just amazed by the variety of dramatic positions and problems and possibilities everyone is facing. Theres something very moving to me about all the late revelations that are not yet so late that they can be ignored, about the deep settling into oneself that makes settling for what doesnt fit no longer acceptable. To be honest, Ive come to feel a great warmth for middle age, and more and more I find myself wanting to be there in my writing.

The climactic scene of the story takes place in amamak, a reinforced safe room, in Tel Aviv. Why did you choose that space for Cohens moment of action and the birth of a baby?

Being in Tel Aviv while rockets are exploded overhead by anti-missiles is a surreal experience. I mean, war itself must always seem surreal. But, in Tel Aviv, what often fascinates me is the way that, a moment after the missiles have been destroyed and the sirens have fallen silent, the whole city snaps back to whatever it was doing right before the emergency began. The conversation that had stopped midsentence resumes, the waiters and waitresses once more sail smoothly between tables, and everything continues as if nothing had happened. This deft restoration of normalcy is itself surreal, the result of a collective refusal to allow a certain aspect of realitythe one where fear and horror liveto take root and unfurl. The shelter, then, where one goes to wait for the danger to pass is, in a sense, the only place where that realitythe reality of death, of the fact that people want to kill and are killedis acknowledged. So it interested me, by contrast, to set a birth there. And not just any birth but one attended to by a man who is returning from his own private excursion into surrealism, courtesy of psychedelics, and descending back into a reality he would rather not face.

Why did you choose to have Cohen be on psilocybin in this scene?

For the reason above. And Id add that in this scene hes actually coming down from his trip. Like sex, psychedelics are easier done than written about. Its nearly impossible to convincingly describe the specific experiences one has had on psilocybin because an aspect of sobriety is skepticism, and skepticism is completely annulled by psychedelics. Everything one feels and experiencespositive or negative, beautiful or scaryis wholly felt and believed. Doubt requires distance, and there is no distance in a psychedelic experience, no stepping back or away. But then one has to come down, and that return, I suppose, is what I was interested in writing aboutthat middle zone where one has not yet lost access to that state of being and belief, even as one is recalled to a reality that cant fully host it. When Cohen is confronted with, as they say, the miracle of life, he hasnt yet lost his sense of wonder, his belief in his own goodness; he hasnt yet been reminded of his own failures, so he can half believe himself to be a part of the miracle.

Cohen feels that he has played a momentous role in the delivery of Navas babyand, of course, physically, he has. But, since we see everything in the story through his eyes, its difficult to know how Nava feels about what happened. Do you have an idea?

Of what Nava feels for Cohen and his part? In the grand scheme of her own experience, probably not all that much. Giving birthtalk about a totalizing experience. Talk about be here now! I dont know of another sober experience more self-absorbing than labor. Everyone elsethe nurses, the doctor, even the fathersort of fades away offstage, as far as I recall, and you are alone inside this enormous event. Which is ironic, because the moment you give birth you cease to be the main protagonist of your own life. Your child takes up that role, and you fall back to play all the other parts. So the labor of delivery is your last chance to be the star of your own life, at least for a very long while.

The story is written in the third person, but, as discussed, its more or less Cohens internal monologue. What appeals to you about writing from that perspective?

Theres a line in the story: between Cohen and Cohen something else had slipped in, courtesy of the perspective of middle age: a hand span of ironic distance. I think its that hand span of distancenot too much and not too littlethat also attracts me to a close third person. The photographer Diane Arbus once described how everyone has a need to look one way but is always seen in another. This space between what we want people to know about us and what we cant help people knowing about us she called the gap between intention and effect. And its that gap that a close third-person perspective bridges, allowing for irony and a touch of humor.

Shelter reminds me a little of your story Zusya on the Roofanother narrative in which a man at a turning point in his life is confronted with the so-called miracle of birth and deeply affected by it. Why do you think this is such a rich subject for you? What do Brodman, the protagonist of Zusya, and Cohen have in common?

A writer friend of mine described the character of Cohen as one of my less ruined men. Its true that theres a certain kind of stymied character that interests me, though not so much for his failure or his ruination as for the moment when he suddenly sees, shining up ahead, a way out. It allows for a story that both looks back at a life and looks forward into the future, a view that can be heady, even breathtaking. Whether the escape or the solution is real or notwhether he actually transcends what he feels bound or oppressed byinterests me less than the encounter with possibility. The chance for redemption: isnt that finally the great subject of all literature?

Read the rest here:

Nicole Krauss on Death, Birth, and Middle Age - The New Yorker