By Matt Smith
WebMD Health News
Reviewed by Brunilda Nazario, MD
Jan. 13, 2017 -- The long, strange trip of research into the benefits of hallucinogenic drugs may be taking another turn.
They've mostly been banned for decades, but in the past 15 years, drugs like LSD, psilocybin (the active ingredient in "magic mushrooms"), and MDMA, also known as ecstasy, have shown promise in treating conditions like depression, post-traumatic stress disorder, and addiction.
Researchers are also looking at legal but widely abused drugs like ketamine, an anesthetic that also can produce hallucinations. The FDA recently put the ketamine-based drug esketamine on the fast track for approval as a treatment for major depression.
Matthew Johnson, PhD, a research psychologist at Johns Hopkins University, says he'd be surprised if hallucinogenic drugs didn't have a proper medical use "under some constrained, limited circumstances."
"Most powerful substances that we know of, that have powerful effects on the central nervous system, are like any powerful tool," says Johnson, who has studied how psilocybin affects depression. "They can have dangerous effects, or beneficial effects, if judiciously used in a context where the dangers are known and mechanisms are in place to address them."
Among some of the recent work:
- In early December, the FDA gave initial approval to plans for a phase III clinical trial of MDMA to treat post-traumatic stress disorder. The study, by the Multidisciplinary Association for Psychedelic Studies (MAPS), is expected to involve 230 people over 2 to 3 years.
- Also in December, a team at Johns Hopkins, including Johnson, released results of a study that tested psilocybin in a group of 51 cancer patients who had symptoms of depression and anxiety. They found high doses -- roughly two to three times the typical recreational dose -- sharply reduced those symptoms, and four out of five had "clinically significant decreases in depressed mood and anxiety" 6 months later.
- Researchers at London's Imperial College used a variety of scanning techniques to map for the first time how the brain responds to the effects of LSD. In March, they reported that the drug's effects correlated with "marked changes" in blood flow and the brain's communication network, giving scientists new insights into the physical responses it produces.
- In 2014, a Swiss-led study found that low doses of LSD, combined with psychotherapy, reduced anxiety in a study of a dozen patients with life-threatening diseases, "suggesting that larger controlled studies are warranted."
Feelings About Drugs Are Changing
The new studies come at a time when attitudes toward drugs are shifting dramatically. The widespread abuse of prescription opioid painkillers is widely discussed as a public health issue rather than strictly a matter for police, while eight states and the District of Columbia have legalized recreational marijuana. After it was asked by some members of Congress, the Drug Enforcement Administration postponed plans to ban the herbal supplement kratom, which scientists say may be useful to combat addiction and chronic pain.
Johnson says researchers are "in our infancy" in figuring out how hallucinogens may help. Like most antidepressants, the drugs affect how the brain uses serotonin -- a chemical related to mood, memory, and sleep. But unlike antidepressants, hallucinogens appear to change how different parts of the brain communicate with each other, Johnson says. That may be why many people who have taken hallucinogens come away with "a radically altered sense of self" and a greater sense of open-mindedness, he says.
What researchers are trying to understand is how long-lasting those brain changes may be, and how that might help with depression, anxiety, and addiction.
MDMA in particular produces a euphoric effect and increases empathy and emotional openness, says Brad Burge, a spokesman for the California-based MAPS. Those traits can help ease the state of "constant hyper-arousal" that PTSD patients have as they try to beat back memories of their trauma, he says.
Burge says the MDMA being tested is nothing like what is commonly sold as "ecstasy" or "Molly" on the street. Those are cut with other substances, such as methamphetamine or other psychoactive drugs like ketamine, and one analysis of seized drugs found nearly half contained no MDMA at all.
Study participants will have a series of psychotherapy sessions and receive the drug twice during the study period. The idea is to provide a "chemical safety net" for patients, "where they can talk and process those feelings more openly," Burge says.
"They're less afraid," he says. Their trauma "becomes something they can think about and talk about and process in a more open way. It's not just an instantaneous cure in these experimental sessions, but follow-up sessions without MDMA are also important to making sure that people are able to take those lessons and really internalize them. People don't just go home and everything's fine."
The drug's effects typically last 4 to 7 hours, with side effects that can include muscle tension, increased blood pressure, and occasional anxiety. Because of that, participants will stay at a clinic overnight after getting the drug, Burge says.
The group hopes to start its trial in mid-2017, he says.
'A Lot of Hoops to Jump Through'
Not everyone responds well to the sensory distortions the drugs produce. They sometimes result in deep distress, anxiety and terror -- the proverbial "bad trip." In addition, the physical effects of the drugs can include increased blood pressure, nausea, dehydration, and muscle tension.
Because most of the drugs are listed as Schedule I drugs by the DEA -- meaning they have no accepted medical use and a high potential for abuse -- getting research studies approved can be difficult, Johnson and Burge say.
Burge says it took his organization 10 years to get research into MDMA to a phase III clinical trial.
"You have an entire array of institutions that need to sign off -- the FDA; the DEA; at a university, the institutional review board," Johnson says. "There are a lot of hoops to jump through."
The FDA allows Schedule I drugs, which include marijuana, to be used for clinical research under a process known as an Investigational New Drug application, agency spokeswoman Sandy Walsh says. When a study gets approved, the drugs involved "are subject to the most stringent restrictions" and have to be stored and kept track of under rules approved by the DEA.
DEA spokesman Russ Baer says anyone who wants to study a Schedule I drug has to submit their proposed research protocols to the agency. Everyone involved in handling the drug has to be registered with the DEA, which judges whether the study plans will keep the drugs under control.
"Since we're not scientists, we're not evaluating the veracity of the scientific research project," Baer says -- that's the job of the FDA and any other research agencies involved. "What we're required to do is to make sure there are appropriate safeguards in place to ensure security protocols are maintained, to make sure any controlled substance is not subject to theft or diversion from legitimate science on one hand to the black market on the other."
There are more than 400 research projects now underway involving marijuana alone, Baer says, and he's not aware of any drug study the agency has rejected or halted. In addition, he said the agency has been having talks with scientists about streamlining the agency's approval process.
"We support scientific research. We want to remove any sort of bureaucratic hurdles that may have existed in the past," Baer says.
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