Members of the scientific community are pushing back on an attempt to criminalize two substances it says are critical to psychedelic research. The move has puzzled experts who say the federal government lacks evidence of the drugs’ widespread use or danger.
There is “no evidence that people are using it recreationally,” said Kat Murdi, executive director of Students for Sensible Drug Policy (SSDP), a group advocating against scheduling the substances.
In 2022, the Drug Enforcement Administration (DEA) said it planned to schedule 2,5-dimethoxy-4-iodoamphetamine (DOI) and 2,5-dimethoxy-4-chloroamphetamine (DOC). The chemicals, created in the 1970s, are currently unscheduled, meaning they are legal for purchase and use. The DEA plans to move them to Schedule 1 alongside drugs like LSD, psilocybin and (at least for now) cannabis.
The federal government classifies such substances as having “no currently accepted medical use” and a “high potential for abuse.” As evidence, they cite the drugs’ similarity to dimethoxy-4-methamphetamine (DOM), which is already a Schedule 1 hallucinogen.
“In humans,” the DEA wrote in its 2023 filling, “anecdotal reports suggest that DOI and DOC produce classic hallucinogenic effects that are similar to DOM, including visual and auditory hallucinations, fatigue, headache, gastrointestinal distress, insomnia and anxiety. … It is reasonable to assume that DOI and DOC have substantial capability to be a hazard to the health of the user and to the safety of the community.”
DOI and DOC are hallucinogenic, experts say, but very different from shrooms or acid. They activate just one of the brain’s 14 serotonin receptors, said Scott Thompson, director of CU Anschutz’ Brain and Behavior Innovation Center, whereas other psychedelics turn on all 14. That leads to a “rather unpleasant” high, Thompson said.
That’s also why the substances are so prized in research: They target the sole receptor that creates a “trip,” which allows for controlled research.
“It is a silver bullet,” Thompson said. “If you are doing a research study, it’s a very powerful, useful tool.”
DOI and DOC have been used to help study anxiety, depression, substance use disorder and more. The drugs have been cited in more than 900 published studies, according to Murdi. In July, SSDP and others sued to force the DEA to allow expert testimony from researchers during the upcoming hearing.
“They’re really contributing significantly to our understanding of how our brains work, particularly when it comes to serotonin,” Murdi said.
If DOI and DOC, part of the DOx class of amphetamines, become Schedule 1 substances, universities would need a special license to use them in research. This process is “prohibitive” in both cost and time, Murdi said. Alaina Jaster, a postdoctoral scholar of psychiatric and behavioral neuroscience at Wayne State University who studied psilocybin and DOI in mice, said her colleagues are currently waiting six months to a year to complete the DEA process.
Even labs with Schedule 1 clearance will have to update their license, according to Jaster.
“You have to renew that licensure for any new drug you add to it,” she said. “Any changes to your license, you have to put all your research on hold.”
The DEA declined to make officials available for an interview. In response to emailed questions, a spokesperson wrote, “It is difficult to determine an average length of time as they all differ.” For Boulder Weekly’s other questions, officials pointed to DEA filings submitted as part of the scheduling process.
A hearing has been scheduled for Nov. 12-22.
Opponents of scheduling DOI and DOC have questioned the agency’s evidence of the drugs’ harms and widespread use in the U.S., which includes “anecdotal reports on the internet,” according to a December 2023 filing by the DEA.
Reported harms include an unspecified number of emergency room visits when used with other unspecified drugs referenced by the DEA and just “three published reports” of “adverse events associated with DOC including, but not limited to, seizures, agitation, tachycardia, hypertension, and death of one individual” since 2008.
The DEA’s filings cite three deaths and 16 “non-fatal intoxications” in Europe since 2008 associated with DOC; “To date, there are no reports of distressing responses or death associated with DOI in medical literature,” it states. The United Nations has listed DOC as a Schedule 1 substance since 2019, though not DOI; DEA officials have argued that the U.S. has to comply with this listing due to an international treaty.
C. Michael White, PharmD, distinguished professor and chair at the UConn School of Pharmacy, agrees there are some dangers to DOI and DOC.
“The dosing of the DOx substances is tougher to nail down,” White wrote in response to emailed questions. “If you overdo it, there are a lot of risks, versus psilocybin and LSD.”
“They can cause teeth grinding (which can result in tooth damage with chronic use), hypertension and racing heart rate (which can increase the risk of heart attacks and strokes), and the risk of seizures.”
Trips on DOx drugs tend to last longer than with psilocybin or LSD, according to White. And unlike MDMA, “there does not seem to be any oxytocin release (with a feeling of close bonding).”
“New people to psychedelics generally tend to not like this DOx experience,” White wrote.
On that, Murdi, Jaster and Thompson agree. That factor alone limits the potential for DOI and DOC to become popular street drugs like other psychedelics.
Said Jaster: “Even the most psychonaut people you’ve met, they’ll say, ‘I did it once and never want to do it again.’”
“It has no recreational purposes or value,” Thompson added. “The whole [DEA] process has been baffling for all of us.”