Standardizing the measurement of psychedelic side effects; Doctor charged in Matthew Perry’s death pleads guilty; and predicting a trip’s outcome
Plus: LSD and MDMA use decreasing and microdosing ketamine to stave off opioid withdrawal
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.
Standardizing the measurement of psychedelic side effects
Psychedelics can produce a variety of side effects. Some, like visual distortions, are commonly expected, and may, in fact, be desirable. Others, like lingering feelings of impending doom or bladder issues, are not sought out or as widely documented. While psychedelics clinical trials usually track side effects, there is no systematic list of effects to ask about or standardized method for collecting this data, which can make it difficult to compare across studies. In a new paper published in the Journal of Affective Disorders, Swiss researchers Abigail Calder and Gregor Hasler present a new assessment of psychedelic adverse effects called the Swiss Psychedelic Side Effects Inventory (SPSI), which they offer as a new tool for documenting adverse effects.
The SPSI lists 32 potential side effects, which includes physical side effects such as nausea and diarrhea, as well as mental ones, like paranoia and “fear of losing your mind or going insane.” The inventory asks participants to rate the severity of each symptom as mild, moderate, or severe. It also asks participants to state their degree of confidence that a particular symptom is directly attributable to their psychedelic experience; for instance, a participant might give a symptom a rating of 0 if they are not sure whether it was caused by their trip, or a rating of 4 if they are certain a symptom was the result of psychedelic use.
Calder and Hasler recommend clinicians use the SPSI multiple times over several weeks after a participant’s psychedelic trip. “Though most side effects emerge before the drug is eliminated from the body, some can appear weeks later, possibly as part of a stress response to extremely frightening psychedelic experiences,” they write. “Additionally, some side effects are usually benign in the acute phase but become worrisome when they last longer, and the reverse can be true when effects that initially seem negative were part of a beneficial therapeutic process in retrospect.”
Doctor charged in Matthew Perry’s death pleads guilty
Last Friday, physician Mark Chavez pleaded guilty to charges of conspiring to distribute ketamine. Chavez is one of two doctors who allegedly provided ketamine to Friends star Matthew Perry, who died of a ketamine overdose in October 2023. The Associated Press reports that Chavez will cooperate with prosecutors in their cases against two others accused of illegally selling ketamine to Perry.
The case has led to increased scrutiny of ketamine prescribing practices from the U.S. Drug Enforcement Administration, whose top administrator spoke out recently about prosecuting medical professionals diverting or overprescribing ketamine. So far, federal authorities have charged five people in the case. Chavez is the third to plead guilty. Perry’s personal assistant, Kenneth Iwamasa, and TV producer Erik Fleming, have also pleaded guilty. Fleming claims he obtained the drug from Jasveen Sangha, who prosecutors allege is a drug dealer known as the “Ketamine Queen.” According to Reuters, Sangha and Salvador Plasencia, another doctor charged in the case, will stand trial in March.
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Predicting a trip’s outcome
The effects of LSD can vary widely between people, and a new study published this week in Translational Psychiatry reviewed data from over 200 participants in LSD studies to understand what factors might predict people’s experiences. They probed the relationship between variables including gender, previous experience with hallucinogens, age, mood before entering LSD sessions, expression of an enzyme involved in the metabolism of LSD called CYP2D6, and personality factors such as extraversion and neuroticism.
The researchers, all affiliated with the University of Basel in Switzerland, found that the most important factor, unsurprisingly, was the size of the dose. Larger doses were correlated with higher likelihood of bad drug effects, good drug effects, and higher scores on the mystical experience questionnaire, as well as nearly every other type of subjective effect reported by participants. People who reported high levels of general well-being before a trip were more likely to report experiencing hallucinations, insightfulness, and a “blissful state,” while those who reported feeling anxious before their trip were also more likely to report feeling anxiety during their trip. People with lower levels of expression of CYP2D6 were more likely to report feeling anxious. Additionally, older people in the study were more likely to report unwanted effects. “Psychedelic experiences have the potential to be life-changing and very challenging, so having well-prepared individuals is crucial for positive clinical outcomes,” the authors write. “By understanding and reinforcing these predictors towards the potential positive effects like ‘Oceanic Boundlessness’ and mystical-type experiences, we may not only bolster therapeutic efficacy but also reduce the likelihood of adverse effects.”
LSD and MDMA use decreasing while use of other psychedelics is increasing
The use of hallucinogens remains at historically high levels, according to a recent report funded by the National Institute on Drug Abuse. The Monitoring the Future survey, conducted by scientists at the University of Michigan, has tracked drug use since 1975 by polling junior high and high school students and following them into adulthood. In last year’s report, the researchers found that 4.1% of adults between 35 to 50 said they’d used psychedelics such as LSD, MDMA, mescaline, or psilocybin in 2022, which then represented an all-time high; that figure ticked up to 4.2% in 2023. Adults between 19 and 30 also reported increased hallucinogen use, from 8% in 2022 to 8.9% in 2023.
According to the report, the rise in psychedelic use is driven by drugs other than LSD. Over the last five years, fewer people say they’ve used that drug; additionally, the number of young adults report using MDMA has been trending downward over the last five years. While the report did not specify which drugs were driving this increase in hallucinogen use, the other drugs included in the survey’s hallucinogen category include mescaline, peyote, psilocybin, and PCP.
Microdosing ketamine to stave off opioid withdrawal
Recently, researchers have proposed psychedelic drugs as a treatment for opioid use disorder. Most of those treatments rely on full-blown trips. But a new pilot study suggests patients undergoing treatment for opioid addiction could benefit from small doses of ketamine that don’t induce dissociative effects.
In the study recently published in Addiction Science & Clinical Practice, the researchers prescribed small doses of ketamine to patients who were trying to transition from fentanyl to buprenorphine, a common but also habit-forming synthetic opioid used to treat opioid addiction, or who had already made the transition to buprenorphine but were experiencing withdrawal symptoms. (Opioid withdrawal symptoms include vomiting and cramps, and can lead to relapse.) The doses were just 16mg, which the authors characterize as an imperceptible dose. For reference, that’s about half as much as the smallest doses used in clinical trials using ketamine to treat depression.
Of the 37 patients prescribed ketamine, 24 of them filled the prescription and took ketamine. Sixteen of those 24 successfully started on buprenorphine, and twelve stayed on buprenorphine for 30 days. Many patients said that withdrawal symptoms resolved within 30 minutes of taking ketamine, and relief lasted for hours. The researchers say that while larger, more carefully designed studies are necessary, this method holds promise. “Widespread off-label use of this inexpensive medication to assist buprenorphine initiation could lower the barrier and increase uptake of a life-saving treatment,” they write.
Lykos Therapeutics announced yesterday that two pharmaceutical industry veterans would assume senior management roles at the company. Michael Mullette, who worked at Sanofi and Moderna before becoming Lykos’s COO in 2022, will be the company’s new CEO, and David Hough will serve as the company’s new chief medical officer. At Psychedelic Alpha, Josh Hardman interviewed Hough, who oversaw the development of Spravato, Janssen’s FDA-approved ketamine nasal spray, and will now oversee Lykos’s MDMA research. Hough discussed the parallels he sees between that medication and other psychedelics, as well as other clinical trial design issues, such as functional unblinding and the role of psychotherapy.
The National Institute on Drug Abuse has awarded a $2.4 million grant to researchers studying how psychedelics could treat methamphetamine addiction.
Ezra Klein interviews writer Jia Tolentino about parenting and finding meaning — and how that relates to psychedelics.
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