MAPS submits FDA application for MDMA; Will state and federal psychedelics laws collide? And what makes 5-MeO-DMT atypical?
Plus: Revised California ballot initiative and new Australia quality standards for MDMA and psilocybin
Happy Friday, and welcome back to The Microdose, an independent journalism newsletter brought to you by the U.C. Berkeley Center for the Science of Psychedelics.
MAPS submits FDA application for MDMA
On Tuesday, the MAPS Public Benefit Corporation (PBC), the for-profit drug development arm of the non-profit psychedelics organization MAPS, announced that it submitted a new drug application to the U.S. Food and Drug Administration. If the FDA approves the application, MDMA could become a prescribed medication used in the treatment of post-traumatic stress disorder. MDMA is currently a Schedule I drug, which by U.S. Drug Enforcement Administration standards means it has “no currently accepted medical use and a high potential for abuse.” But if MDMA is approved by the FDA as a medication, that would likely prompt a reevaluation of that Schedule I classification.
The application comes on the heels of results from MAPP2, the second MAPS-sponsored phase 3 clinical trial investigating the use of MDMA-assisted therapy to treat PTSD. That study was published in Nature Medicine in September, and at the time, MAPS said they’d planned to submit new drug application by the end of the year. Considering both of MAPS’s phase 3 clinical trials, researchers studied nearly 200 participants and concluded that MDMA-assisted therapy was more effective in treating PTSD than a combined placebo and therapy.
In a press release, MAPS PBC says that they’ve requested priority review for their application, which means that the FDA would have 60 days to either accept or reject the application for review, as well as to determine whether it will prioritize the application’s review. If the FDA prioritizes the application, the agency will take action within six months. If it is not prioritized, standard review takes around 10 months. Either way, MAPS PBC will likely receive a ruling on their application sometime in 2024 unless the FDA requires further information.
Will state and federal psychedelics laws collide?
In the U.S., only Oregon and Colorado have passed ballot initiatives to create state-legal psilocybin service programs. However, other states, including Massachusetts, are considering similar initiatives. In an opinion piece published in JAMA this week, attorney Mason Marks describes why he believes state-regulated programs “are on a collision course” with federal law.
He points out that the U.S. Food and Drug Administration has already taken legal action against companies that are marketing unapproved medical and therapeutic uses for drugs like kratom, an herbal supplement that can produce stimulant-like effects, and ketamine. While Oregon’s program explicitly disallows businesses from making “curative or therapeutic claims” about psilocybin, some businesses are advertising psilocybin sessions as therapeutic or claiming the substance can treat depression and anxiety. “If the FDA issues warnings for legal products such as store-bought kratom and physician-prescribed ketamine, it will likely object more strenuously to medical marketing of Schedule I drugs such as psilocybin,” Marks writes. Of course, this is an opinion piece; to date, the FDA has not publicly indicated what, if anything, the agency intends to do related to psilocybin services in Oregon.
Marks also raises concerns that medical professionals could face legal penalties if they don’t disclose their use of psychedelics in treatment. He alleges that some members of Colorado's Natural Medicine Advisory Board, which is drafting rules for the state’s psilocybin program, “have even suggested clinicians could provide psychotherapy alongside psilocybin products and bill Medicaid only for psychotherapy by using existing billing codes,” Marks writes. “But billing Medicaid for those services under therapy codes and intentionally omitting the use of psychedelics could potentially violate the federal False Claims Act or constitute health care fraud, which is a crime.”
In his newsletter On Drugs, attorney Matt Zorn shares some of Marks’s concerns. “Whether any federal crackdown will occur, only time will tell,” he writes. “Bottom line: if you are a medical professional flirting with these new systems, be careful.”
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What makes 5-MeO-DMT an atypical psychedelic?
A new paper published in Psychopharmacology this week lays out a theory for why the tryptamine 5-MeO-DMT is unlike other psychedelics. 5-MeO-DMT is perhaps best known as a psychoactive molecule in secretions from Incilius alvarius, a toad found in the southwestern U.S. and northwestern Mexico. Celebrities including former boxer Mike Tyson have spoken publicly about their experiences smoking the dried secretions, which prompted the National Park Service to issue a warning on social media requesting that park visitors refrain from licking the toad. The substance can also be synthesized in labs. Whether natural or synthetic, it has a rapid onset and is associated with the frequent occurrence of a complex and poorly understood phenomenon called “reactivation,” which is similar to what’s often called a flashback.
The researchers review previous studies for clues about the mechanisms of action of 5-MeO-DMT and how it could be different from that of other psychedelics. Psychedelics act on serotonin receptors such as 5-HT1A and 5-HT2A. The subjective effects of psilocybin and LSD are primarily due to action at 2A receptors, while 5-MeO-DMT has a higher affinity for 1A receptors. Previous research suggests that 1A receptors are associated with seizure disorders, which squares with anecdotal reports cited by the researchers of animals and one human child having seizures after ingesting 5-MeO-DMT. That could also explain why some 5-MeO-DMT users report experiencing involuntary body movements. The researchers write that such reactions could actually be related to the therapeutic effects some people report after using 5-MeO-DMT; epileptic symptoms can be similar to electroconvulsive therapy, which is sometimes used to treat mood disorders.
“If the current hypothesis is supported, epileptiform activity would not preclude 5-MeO-DMT in the treatment of mental health conditions, just as generalized seizures do not preclude electroconvulsive therapy in the treatment of mood disorders,” the authors write. “Rather, confirmation of epileptiform activity associated with 5-MeO-DMT use would allow for optimizing best practice to maximize efficacy and safety.”
The State of Psychedelics: Revised California ballot initiative
The creators of California’s Psychedelic Wellness and Healing Initiative ballot measure submitted final text for the proposal to the State Attorney General for consideration on the 2024 ballot. The measure was created by Dave Hodges, founder of Oakland’s psychedelics Church of Ambrosia. Zide Door, the church’s Oakland location, was raided by Oakland Police in 2020 after receiving tips that it was selling unlicensed cannabis.In a 2022 interview with VICE, Hodges said that the organization charges members $5 to receive the church’s sacraments: cannabis and psilocybin mushrooms.
The initiative proposes a radical set of changes to state drug policy. Those changes include making it state-legal for adults to sell, possess, prepare, grow, gather, gift, and transport a variety of psychedelics found in plants and fungi. It also proposes reversing criminal charges related to the state’s list of hallucinogenic drugs and allowing healthcare practitioners to recommend entheogenic plants and substances to treat health issues and churches and Indigenous groups to use psychedelics in ceremony.
The text submitted to the Attorney General was revised from a version of the initiative we reported on in early November. The revised draft removes a statement requiring individuals or groups from having entheogenic substances tested in a lab, and it includes a new clause requiring any entheogenic business with 50 or more employees to hold an annual secret ballot to vote on unionization. To qualify for the November 2024 ballot, the initiative will need to collect over 546,000 signatures by April.
New Australia quality standards for MDMA and psilocybin
Last Friday, Australia’s Therapeutic Goods Administration proposed new quality standards for MDMA and psilocybin, which can now be prescribed in the country by authorized psychiatrists for PTSD and treatment-resistant depression, respectively. The standards would allow synthetic psilocybin, and just one species of naturally-occurring psilocybin-containing mushrooms to be prescribed: Psilocybe cubensis. (P. cubensis is also the only species allowed for use in Oregon’s psilocybin services program.) The proposal also lays out standards for testing and labeling the drugs. The government will be accepting public comment on the proposal through January 2024.
The Daily Beast profiles doctoral candidate Zeus Tipado, who is studying the potential therapeutic effects of combining DMT and virtual reality.
In The Guardian, journalist Shayla Love explores what connects psychedelics and the pursuit of lifespan extension.
State and local leaders in Oregon have proposed rolling back Measure 110, a drug decriminalization ballot initiative state voters passed in 2020 alongside Measure 109, which established psilocybin services in the state. The initiative did away with penalties for possession of small amounts of drugs including methamphetamine, heroin, and fentanyl, but officials are now proposing a ban on public use of these drugs, The New York Times reports.
In Ecstatic Integration, Jules Evans covers the sleep issues some psychedelics users report after tripping.
Journalist Mattha Busby reports in VICE that Mexican drug cartels are kidnapping and killing people harvesting psychedelic secretions from Incilius alvarius toads.
You’re all caught up! Have a great weekend. This will be the last news round-up of 2023, but we’ll be back in your inbox on Monday with a new issue of 5 Questions. Wishing you a peaceful end of the year!
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