FDA – Page 2 – Go Retire Psychiatrist

DEA to Reschedule Marijuana or Not?

I’ve seen an article posted in February of this year on the American Veterinary Medical Association (AVMA) about there being a plan afoot to change marijuana from DEA Schedule I to III or remove it from the Controlled Substances Act. I couldn’t find out anything about it except in in the AVMA article.

I can’t find what the FDA, HHS, or the DEA may or may not be doing as far as taking any action on about this, if any. I think it’s interesting that the AVMA reports the HHS plan to ask the DEA to change the scheduling of marijuana was “leaked” to the news outlets. There is a link to a New York Times story about it. I guess that’s better than nothing, though some might argue the point.

The AVMA article also linked to a letter from several members of congress urging the DEA to change the scheduling of marijuana, remove it from the Controlled Substances Act or risk getting their knuckles rapped with a ruler by Senator Chuck Schumer. Huh, what’s up with that?

I looked at the HHS website and found nothing suggesting that they are going after the DEA with a fire hose to get this done. The DEA is not mentioning anything about the project on their Drug Information web page.

The only ones talking about this publicly so far are the banks, the weed growers, and the AVMA as far as I can tell. The impression I get is that something is going to happen in a matter of months about decriminalizing and rescheduling marijuana. Things usually don’t happen that quickly in government.

I thought I was finished with this post until yesterday when I read U.S. Senator Mitt Romney’s letter to the DEA urging it not to move marijuana from Schedule I to Schedule III because it would violate something I needed to learn more about, which is an international treaty called the Single Convention.

The Single Convention was ratified by the U.S. Senate in 1967 and it’s part of an international treaty which says marijuana must remain classified as either Class I or II—until a congressman can clearly demonstrate the ability to walk heel to toe in a straight line for a distance not less than 10 yards after smoking a standard large bong of high-grade marijuana.

One thing I can gather from Senator Romney’s letter is that it verifies HHS’ did in fact recommend that the DEA reschedule marijuana.

The FDA Announcement on Kratom

Just in case you missed it, the FDA posted an announcement about Kratom in February this year. According to the FDA:

“Kratom is a tropical tree (Mitragyna speciosa) that is native to Southeast Asia. Products prepared from kratom leaves are available in the U.S. through sales on the Internet and at brick-and-mortar stores. Kratom is often used to self-treat conditions such as pain, coughing, diarrhea, anxiety and depression, opioid use disorder, and opioid withdrawal.”

The other day as we were driving home on Highway 1 through Iowa City, I saw a sign advertising Kratom on a small store. I thought that might be illegal, but when I checked the Iowa Office of Drug Control and Policy, I found out it’s currently legal in the state.

Opinions vary about risks of using Kratom. The DEA tried to place in on the Schedule I, but the American Kratom Association and other supporters apparently prevented that simply by protesting it. The pharmacist who wrote the article (link above) raised a note of irony by questioning why marijuana is still regulated as a Schedule I drug.

The legality of Kratom also varies across the country. There is a very detailed review article about it that attempts to examine the use of Kratom from both the medical practitioner and patient points of view.

Picture Credit: By Psychonaught – Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=8255742

New Compound MM-120 Related to LSD Gets FDA Nod

I saw the story in Psychiatric Times about the compound MM-120, which the FDA recently granted breakthrough designation. MM-120 is related to LSD. Breakthrough designation is defined by the FDA as, “…a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).”

The compound is made by the company MindMed. This is not to be confused with mind meld, a Star Trek thing related to Vulcans like Spock who can do this telepathic touch thing. The MindMed organization made MM-120 to help treat people who suffer from Generalized Anxiety Disorder. Their study shows the drug could be used as a standalone treatment for the disorder.

According to one story about it published in the December issue of Drug Discovery and Development, it’s not likely MM-120 will be stocked in pharmacies next to the antihistamines and decongestants. The authors believe it would be more likely included in a Risk Evaluation and Mitigation Strategies (REMS) program.

This brings back nightmares about the Clozapine REMS program, which many psychiatrists found almost impossible to enroll in several years ago because of glitches in the web-based application. In fact, the FDA was still not happy with it a couple of years ago, to the extent they had to “temporarily exercise enforcement discretion” over aspects of the program.

Anway, the article goes on to say that the drug has a pretty good safety profile, although concede that the study found the higher dose of MM-120 led to “…perhaps some more challenging experiences….” There were no incidents of suicidal or self-injurious behavior.

I wonder what the “challenging experiences” were, exactly. After all, MM-120 is basically LSD, which was invented in 1938 by the Swiss chemist, Albert Hofmann. He was doing research into crop fungus. He thought it could be used to treat mental illness, even after he accidentally ingested some of it and hallucinated a future in which a guy named Timothy Leary would advise everyone to “turn on, tune in, drop out.”

That whole fungus research issue reminds me of the still unsettled question of how a whole town in France got higher than a kite (leading to some deaths) back in 1951. Ergot poisoning was the initial theory, although later somebody believed it might have been perpetrated as a secret LSD experiment by the CIA. I think the mystery is still unsolved.

However, there is also the history of MK-Ultra, which apparently actually was a classified CIA project running during the Cold War which involved giving LSD to certain unlucky subjects, some of whom didn’t know they were getting it—with disastrous results in some cases.

Just to let you know, I don’t suspect there is some conspiracy between extraterrestrials and the pentagon to get the world population so confused on LSD that we start believing all those crop circles are being created by two guys using a board and a rope. Forget what Agent Mulder says.

FDA Issues Warning Not to Use Tianeptine

There have been several warnings from the FDA and others for several years (going back to at least 2014) against using tianeptine. It’s used as an antidepressant in other countries, but “FDA is warning consumers not to purchase or use any Neptune’s Fix products, or any other product with tianeptine — a potentially dangerous substance that is not FDA-approved for any medical use but is illegally sold with claims to improve brain function and treat anxiety, depression, pain, opioid use disorder and other conditions.”

Tianeptine has been called other names including Neptune’s Fix, Zaza, Coaxil, Stablon, Tianna Red, and others.

It reportedly has been banned in several states. Southern Iowa Mental Health Center published an educational web page in 2022 indicating that a review between 2000 and 2017 found a sharp untick in tianeptine-related poisoning calls during that time period.

The web page also pointed out that “The study specifically noted that while the drug was implicated in just five poisoning calls back in 2014, that figure rose to 38 in 2015, 83 by 2016, and 81 by 2017. And most of those calls involved relatively young people, between the ages of 21 and 40.”

Phenylephrine Spelled Backwards is Enirhpelynbehp

News headlines are screaming about class action lawsuits being filed against drug companies selling the oral form of a nasal decongestant that the FDA says doesn’t work. It’s called phenylephrine. Phenylephrine has been around since the early 1970s and it’s a common ingredient in over-the-counter (OTC) cold remedies found in grocery stores in the medicine aisle.

The FDA advisory committee met on September 11-12, 2023 about phenylephrine-containing oral products and there is a clarification of the FDA committee’s decision to identify them as ineffective that was posted on September 14, 2023.

A common OTC containing the agent is Sudafed PE. The Equate version of it is Suphedrine PE, which is cheaper. The name capitalizes on its similarity to the name Sudafed, which is pseudoephedrine—which is an effective oral agent for relieving nasal congestion. The problem with it is that it’s been behind-the-counter since 2006 because it can be used in the manufacture of methamphetamine.

Sena bought a box of Suphedrine PE the other day because she caught a head cold. She thinks it’s helplful.

I took a quick look at a few of the presentations of the FDA Advisory Committee meeting. Mainly I just noted the last slide of the FDA presentation, which said that recent studies showed phenylephrine 10 mg was not significantly different from placebo.

Another presentation showed that a large consumer survey indicated that Americans rely on phenylephrine and thought it was an effective nasal decongestant.

This reminded me of Serutan, which is just Nature’s spelled backwards. Serutan was not a placebo; it was a fiber-based laxative, but a lot of people made fun of it. But that, in turn, reminded me of Geritol, which was sold as a tonic a long time ago and which, for a while, was thought by many people to help women get pregnant. Who knows? Maybe some people still believe that, although even the manufacturer disputes the claim.

On the other hand, this in turn reminded me of a medication called Obecalp. You can find many web entries about Obecalp, which is just “placebo” spelled backwards. Some physicians may still be prescribing Obecalp (placebos don’t always have to be pills). In general, the opinion about the ethics of the practice is expressed in a recent paper (Linde K, Atmann O, Meissner K, Schneider A, Meister R, Kriston L, Werner C. How often do general practitioners use placebos and non-specific interventions? Systematic review and meta-analysis of surveys. PLoS One. 2018 Aug 24;13(8):e0202211. doi: 10.1371/journal.pone.0202211. PMID: 30142199; PMCID: PMC6108457.):

“Although the use of placebo interventions outside clinical trials without full informed consent is generally considered unethical [1–3], surveys in various countries show that many physicians prescribe “placebos” in routine clinical practice [4–7].”

There’s actually a fairly large body of research about placebo effects. One really long paper has interesting conclusions and key points (Wager TD, Atlas LY. The neuroscience of placebo effects: connecting context, learning and health. Nat Rev Neurosci. 2015 Jul;16(7):403-18. doi: 10.1038/nrn3976. PMID: 26087681; PMCID: PMC6013051.):

Conclusions:

A substantial part of the therapeutic benefit patients experience when undergoing medical treatment is caused by their brain’s response to the treatment context. Laboratory investigations of placebo effects provide a way of examining the brain mechanisms underlying these effects. Consistent findings across studies include reduced activity in brain areas associated with pain and negative emotion, and increased activity in fronto–striatal–brainstem circuits. In most cases, the creation of robust placebo effects across disorders and outcomes seems to require appropriate conceptual beliefs — maintained in prefrontal cortical networks — that are supported by experience-dependent learning in striatal and brainstem circuits. However, the critical ingredients for eliciting placebo effects, at both the psychological and brain level, are just beginning to be understood. These ingredients may differ substantially depending on whether the outcomes are symptoms, behaviours or changes in physiology. A better understanding of the neuroscience of placebo could yield rich benefits for both neuroscience and human health.

Key Points:

Placebo effects are effects of the context surrounding medical treatment. They can have meaningfully large impacts on clinical, physiological and brain outcomes.
Effects of placebo treatments are consistent across studies from different laboratories. These effects include reduced activity in brain areas associated with pain and negative emotion, and increased activity in the lateral and medial prefrontal cortex, ventral striatum and brainstem.
Placebo effects in pain, Parkinson disease, depression and emotion are enabled by engagement of common prefrontal–subcortical motivational systems, but the similarity across domains in the way these systems are engaged has not been directly tested.
Meaningfully large placebo effects are likely to require a mixture of both conceptual belief in the placebo and prior experiences of treatment benefit, which engage brain learning processes.
In some cases, placebo effects are self-reinforcing, suggesting that they change symptoms in a way that precludes extinction. The mechanisms that drive these effects remain to be uncovered, but doing so could have profound translational implications.

I will probably catch Sena’s head cold. By the way, Phenylephrine spelled backwards is enirhpelynehp.

FDA Rumor Control Website

I just found the FDA Rumor Control website. It contains a lot of helpful information about the misinformation we often find about health care products and diseases like Covid-19, vaccines and more. It’s an eye-opener.

What’s Up with Seasonal Vaccines This Fall?

I just read an interesting article in JAMA on this fall’s Covid-19 vaccine. Most of it is from the FDA meeting in June (Rubin R. This Fall’s COVID-19 Vaccines Will Target Omicron XBB Subvariants, but Who Needs Them Remains to Be Seen. JAMA. Published online July 05, 2023. doi:10.1001/jama.2023.10053).

One expert was quoted, indicating that there will be “…an elaborate discussion” at the CDC ACIP meeting about who should get the new monovalent XBB.1.5 vaccine. I don’t see that the meeting is scheduled yet.

There are some other interesting quotes to pass along:

“Back in March and the first half of April, XBB.1.5 represented more than 80% of circulating SARS-CoV-2 in the US, according to CDC estimates. Its dominance began to slip in late April, and as of late June, XBB.1.5 represented little more than a quarter of circulating SARS-CoV-2 variants. By then, though, XBB.1.5 and 9 other XBB subvariants together accounted for a total of 96% of circulating SARS-CoV-2 in the US. Fortunately, members of the XBB family of subvariants are antigenically similar to each other, so a vaccine against XBB.1.5 should protect against the rest of them as well, the WHO committee noted.”

“By the third quarter of 2022, an estimated 96.4% of approximately 143 000 blood donors in a nationwide, longitudinal cohort had SARS-CoV-2 antibodies from previous infection or vaccination or both, according to an analysis published in June in Morbidity and Mortality Weekly Report.

Or, as Sawyer told JAMA, “[t]he whole US has had this virus in one form or another.”

Because of the high prevalence of SARS-CoV-2 antibodies in the population, Paul Offit, MD, in an interview predicted “a focused recommendation by the CDC” regarding who should receive the XBB.1.5 vaccine.”

“Offit said he expects that the CDC will recommend the new monovalent XBB.1.5 vaccine for groups at the greatest risk for severe disease, reflected in continuing hospitalizations for COVID-19. Those groups likely would include people who are 75 years or older, people with severely compromised immune systems, and pregnant people, Offit said.”

“At least for people 60 years or older, the fall vaccine situation will be more complicated than it was a year earlier, Schaffner noted. That’s because at its regular monthly meeting in June, ACIP voted to recommend that this age group have the option of being vaccinated against respiratory syncytial virus (RSV) after consulting with their physician or pharmacist.”

That would mean that there would be 3 vaccines coming in the fall: RSV, Covid-19, and influenza. Sena and I have been doubtful about why a conversation with a physician would be necessary for the RSV vaccine. We don’t know whether that means you couldn’t get it without a physician’s order. There are also questions about coadministration of the RSV and Covid-19 vaccines.

Because the time is coming soon for seasonal vaccines, we’re hoping the questions will be answered soon.

FDA Meeting Today on Strain Selection for Periodic Covid-19 Vaccine

The FDA Vaccines and Related Biological Products Advisory Committee will meet today from 8:30 am-5:00 pm ET to discuss and make recommendations on strain selection for the periodic updated Covid-19 vaccines for the 2023-2024 vaccine campaign.

The discussion topic will be:

“Based on the evidence and other considerations presented, please
discuss selection of a specific XBB lineage (e.g., XBB.1.5 or
XBB.1.16 or XBB.2.3) for inclusion in the 2023-2024 Formula of
COVID-19 vaccines in the U.S.”

The voting question will be:

“For the 2023-2024 Formula of COVID-19 vaccines in the U.S., does the
committee recommend a periodic update of the current vaccine composition to
a monovalent XBB-lineage?”

UPDATE: The committee upvoted the question unanimously. The word “periodic” was removed from the question. A September 2023 time frame was expected for availability of the new vaccine.

FDA Update on Covid-19 Annual Vaccine Strategy

On April 18, 2023 the FDA posted an update on the Covid-19 updated bivalent vaccine and the upcoming immunization strategy for this fall. According to the announcement:

“In June, the FDA will hold a meeting of its VRBPAC to discuss the strain composition of the COVID-19 vaccines for fall of 2023. Much like the FDA does yearly with the influenza vaccines, the agency will seek input from the committee on which SARS-CoV-2 variants and lineages are most likely to circulate in the upcoming year. Once the specific strains are selected for the COVID-19 vaccines, the FDA expects manufacturers to make updated formulations of the vaccines for availability this fall.”