Colorado could become the second state after Oregon to allow the use of certain psychedelic substances that are illegal under federal law.

But while Oregon voters in 2020 approved the supervised use of psychedelic mushrooms, the citizen initiative on the Colorado ballot in November goes further. Proposition 122 would allow the personal use of psilocybin mushrooms and certain plant-based psychedelic substances by adults 21 and over but would ban sales except in licensed “healing centers,” where people could ingest them under the supervision of trained facilitators.

The psychedelic substances, which can alter a person’s perception and cause hallucinations, are Schedule I controlled substances, which is the federal classification given to drugs deemed to have a high potential for abuse and serve no legitimate medical purpose. However, a still-developing body of research has found that psychedelic mushrooms may have health benefits, such as treating depression.

As of June, 15 cities and other local U.S. jurisdictions have decriminalized possession of psilocybin or deprioritized the policing, prosecution or arrest of users. Denver’s 2019 voter-approved initiative made the adult possession and use of psilocybin mushrooms the city’s lowest law enforcement priority, and it prohibited the spending of resources on enforcing related penalties.

Here are five key things to absorb about the initiative in Colorado:

1. What does the Colorado initiative do?

Proposition 122 is one of 11 statewide ballot measures that Colorado voters will decide in the Nov. 8 general election. The measure would allow adults to grow, possess and use mushrooms containing the chemicals psilocybin and psilocin, and decriminalize three plant-based psychedelics: mescaline (though it specifically excludes the peyote cactus), ibogaine (from the root bark of the iboga tree) and dimethyltryptamine (a compound in ayahuasca brew). It also would require the state to create regulations for facilities where adults 21 and older can buy and take the psychedelics under supervision. Selling the drugs outside of those facilities would remain illegal.

The measure sets a timeline for the regulatory process and facilities to be operational by late 2024 for psilocybin, and the state could expand the list of psychedelic substances to include mescaline, ibogaine and dimethyltryptamine in those facilities starting in 2026. If voters approve the initiative, people who use those psychedelics would be protected from professional discipline or losing public benefits, and criminal records of past convictions for offenses made legal under the measure could be sealed.

2. What are the potential health benefits?

Supporters’ primary argument for the measure’s passage is that psychedelic mushrooms and plants have potential mental health benefits. Emerging research and clinical trials are studying the substances’ effectiveness as an alternative treatment for conditions such as depression, anxiety and post-traumatic stress disorder. Proponents of the measure say regulation would increase access for people struggling to find effective mental health care. They also say psychedelic mushrooms are not addictive and pose no public safety risk.

3. What are the risks and unknowns?

Opponents caution that the measure is too far ahead of the science, and that the still-developing research should not be used to legitimize the legalization of psychedelic mushrooms and plants for medical or recreational use. They also point out that much of the research conducted has involved psychedelic mushrooms, and that relatively little is known about the effects of mescaline, ibogaine and dimethyltryptamine.

According to officials at the Justice Department’s National Drug Intelligence Center, ingesting psilocybin can produce negative physical effects, such as vomiting, weakness and lack of coordination, along with negative psychological effects, such as being unable to distinguish fantasy from reality. Psilocybin can trigger episodes of psychosis, so people with a personal or family history of psychosis are generally excluded from studies. Psilocybin can also exacerbate heart conditions.

Many people claim that because psilocybin is derived from plants (technically, fungi) it is safer than pharmaceutical drugs created in a lab. This distinction has no basis. Many plants are poisonous, and many pharmaceutical drugs are derived from natural substances.

4. What does the science say?

Initial studies have found that psilocybin can help treatment-resistant depression or anxiety and depression in patients with terminal illnesses. While the findings are promising, researchers caution that larger sample sizes and additional research are needed to understand psilocybin’s neurobiological factors and long-term effects. In 2019, the FDA called psilocybin a “breakthrough therapy,” a designation meant to speed up development of promising drugs. No psychedelics have been approved for medical use so far.

Of the drugs being considered in the Colorado initiative, psilocybin is the most studied. Clinical trials have tested psilocybin in combination with therapy. Unlike antidepressants, which must be taken regularly, psilocybin has been shown to have durable treatment effects after just one, two or three doses.

Some research findings show that psilocybin-assisted therapy can be useful in treating substance use disorders, including nicotine and alcohol addiction.

5. Will this sprout another industry like marijuana?

Because psilocybin is naturally occurring, people tend to assume its path to legalization will follow that of cannabis. However, the compounds have key differences in the way they affect people. Psilocybin is unlikely to win approval as easily as marijuana, which is legal for medical use in 39 states and the District of Columbia. Nineteen of those states and D.C. also allow recreational use.

The Colorado measure expressly forbids the sale of psychedelics outside of licensed facilities. However, the potential for legalization in the state and elsewhere in the U.S. has spurred the launch of dozens of companies eager to commercialize the sale and treatment of psilocybin. Some are organizing retreats to Jamaica, Peru or Mexico, where they conduct ceremonies that reflect the traditional use of psilocybin and other natural psychedelics that date back centuries.