New study suggests TrkB receptor is key to psychedelics’ antidepressant effects, U.S. Patent board upholds COMPASS COMP360 patents, and Rhode Island bill advances

Plus: Best practices for addressing spiritual experiences in psychedelic therapy and potential opt-out in Clackamas County, Oregon

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. 

New study suggests TrkB receptor is key to psychedelics’ antidepressant effects

Evidence from clinical trials suggests that psychedelics are associated with antidepressant effects and increased neuroplasticity, the brain’s ability to grow and change — and scientists don’t yet understand why or how. While many studies have posited that psychedelics’ antidepressant effects are a result of acting on the body’s serotonin systems, a new study published on Monday in Nature Neuroscience provides evidence for another mechanism: psychedelics bind to TrkB receptors.

TrkB stands for tropomyosin (or tyrosine) receptor kinase B, often pronounced “track B,” which are receptors for proteins that support neuronal growth. Previous studies found that antidepressants known as SSRIs and ketamine also bind to TrkB. In this study, researchers observed how LSD and psilocin bind to cells expressing TrkB in cell cultures. The psychedelics’ ability to bind with TrkB was 1000 times stronger than that of the SSRIs’ — and when researchers gave mice LSD, the rodents showed fewer signs of depression.

Additionally, the researchers discovered that LSD binding to TrkB was a separate mechanism from the drug’s ability to stimulate a class of serotonin receptors known as 5-HT2A. TrkB activity seems to promote neuroplasticity without any signs of hallucinogenic effects. That finding opens the door to future work in which researchers could theoretically create novel anti-depressant medicines targeting TrkB without generating certain subjective psychedelic effects.

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U.S. Patent board upholds COMPASS COMP360 patents

On Tuesday, mental health company COMPASS Pathways announced that the U.S. Patent and Trademark Office (USPTO) has upheld two of their patents covering a form of psilocybin known as COMP360.  In December 2021, both of the patents were challenged by a non-profit patent watchdog group called Freedom To Operate, or FTO. 

The USPTO denied those challenges, and in response, FTO filed a request for reconsideration with the U.S. Patent Trial and Appeal Board in July 2022. Two weeks ago, the USPTO also denied that request. “COMPASS is pleased with the PTAB’s decision to uphold two important US patents covering the Company’s crystalline psilocybin polymorph A,” said CEO Kabir Nath in the company’s press release. 

FTO had cited peer-reviewed research showing that what COMPASS claimed to be a novel form of psilocybin, which they called “Polymorph A,” is not actually a new, single crystalline form but a mixture of two other well-known polymorphs. They argued that this would render COMP360 unpatentable.

Even though the patent board denied FTO’s challenge, the board’s ruling established a narrowed interpretation of what constitutes the company’s proprietary Polymorph A form of psilocybin. The ruling will still end up limiting the company’s ability to prevent others from manufacturing and distributing the drug, FTO’s director Carey Turnbull told The Microdose. “As a result of the work of FTO and others, manufacturers now have a clear roadmap for ensuring the psilocybin they produce and sell does not infringe COMPASS’s patents,” he said.

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State of Psychedelics: Rhode Island bill advances

On Tuesday, Rhode Island’s House Judiciary Committee voted to pass H5923 out of committee. The bill, first introduced in March, would amend current state law to allow people to possess up to an ounce of psilocybin mushrooms without penalty, and to cultivate psilocybin mushrooms for personal use. It also sets the groundwork for the state to establish rules and regulations for psilocybin medical prescriptions if the U.S. Food and Drug Administration reschedules psilocybin, but that clause would sunset on July 1, 2025. The bill now moves on to the full House for a vote. 

Best practices for addressing spiritual, existential, religious, and theological (“SERT”) experiences in psychedelic therapy

So far, much of the excitement around psychedelic-assisted therapy (PAT) has focused on psychedelics — but now, researchers are suggesting that the field think more carefully about best practices for the therapy part of psychedelic-assisted therapy. “To achieve an evidence-based, effective PAT, the psychotherapeutic components of treatment must be clearly specified, rigorously tested, tailored to mediators and moderators of response, and optimized for safety,” Emory University researchers write in a paper published in JAMA Psychiatry. 

More specifically, the authors believe practitioners must find a way to support psychedelics users’ spiritual, existential, religious, and theological — or SERT — experiences. Those types of experiences likely drive therapeutic effects, they write, and while those effects are “widely acknowledged in PAT treatment manuals, facilitator training, and research methodology, SERT components in PAT have not been systematized and their appropriate administration remains to be clarified.” They recommend that all clinicians be trained to recognize and respond to participants’ spiritual encounters and concerns. The researchers also suggest that clinicians provide culturally-sensitive care, and that clinical treatment teams include people who have been board-certified to be spiritual health clinicians or chaplains. 

The Latest in Oregon: Potential Clackamas County opt-out

This November, voters in Clackamas County, Oregon could be asked to vote on reversing Measure 110 as it applies to their county. The measure reduced drug possession penalties and was passed in 2020 alongside Measure 109, which established state-legal and state-regulated psilocybin services in Oregon. Willamette Week reports that the proposed November 2023 ballot initiative would ask voters whether the legislature should “criminalize possession of certain hard drugs, specifically, heroin, cocaine, methamphetamine, MDMA, LSD, psilocybin, methadone, and oxycodone.’” 

“By including psilocybin, the active ingredient in magic mushrooms, Clackamas County is asking voters to reconsider Measure 109, too,” reporter Anthony Effinger writes. 

• Presenters at the upcoming Psychedelic Science 2023 conference in Denver, CO were asked to sign a contract that includes an “exclusivity window” barring them from performing or participating in psychedelics-related events within 500 miles of Denver between April and August, reports Russell Hausfeld in Psymposia. “These contract clauses represent a broader and concerning trend of limitations on the free and open exchange of ideas at events billing themselves as premier academic conferences while, in reality, behaving like industry-sponsored gatherings,” Hausfeld writes. 

• In a video contest for so-called psychedelic cryptography, contestants submitted videos with messages specifically made to be decoded more easily by people tripping on psychedelics. “The winning videos play on the common psychedelic experience of seeing radiant ‘tracers,’ which are trails of colors and afterimages that linger in the visual field,” according to VICE. To the sober eye, the videos are underwhelming, but the judges were – of course! – high. Here’s the winning entry:

• Shroom-selling business The Mushroom Cabinet opened in Hamilton, Ontario in December 2022, and local police quickly shut it down. According to CBC, it’s open again. "These acts of civil disobedience force governments to act, either to decide to enforce or to move more quickly with respect to what they're going to do around regulation," drug policy expert Akwasi Owusu-Bempah told CBC. “I think we'll see more stores.”

• SF Gate details the wild (and wildly unethical) history of Operation Midnight Climax, the San Francisco brothel the Central Intelligence Agency ran between 1955 and 1963 so federal agents could test LSD on unsuspecting johns.  

• Will Patterson co-founded CareRev, a start-up some called “Uber for nurses” — and employees tell The Information that he claimed he came up with the company idea while high at Burning Man, and that he urged employees to try LSD. He has since resigned as the company’s CEO. 

You’re all caught up! Have a great weekend. We’ll be back in your inbox on Monday with a new issue of 5 Questions — and after that, we’ll be changing up our regularly scheduled programming and bringing you daily dispatches from the Psychedelic Science 2023 conference June 20 through June 23. 

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