Marijuana-Like Compound Banishes Fear

Study Points to New Treatments for Anxiety, PTSD

Medically Reviewed by Charlotte E. Grayson Mathis, MD on August 02, 2002
From the WebMD Archives

Aug. 2, 2002 -- What makes fearful memories go away? It's a natural brain chemical similar to the active ingredient in marijuana, mouse studies suggest.

The findings may lead to new treatments for people who experience overwhelming but inappropriate fear. Such fears are a hallmark of posttraumatic stress disorder (PTSD) and other anxiety disorders such as obsessive-compulsive disorder.

The report in the Aug. 1 issue of the journal Nature focuses on what now is known as the cannabinoid system. It's named after cannabis, or marijuana. Recent studies show that the human body makes its own cannabis-like substances, called cannabinoids. The brain is chock-full of tiny switches -- receptors -- that set off complex chains of events when cannabinoids turn them on. Cannabinoids play important natural roles in pain, in control of movement, and in memory.

Beat Lutz, PhD, a researcher at the Max Planck Institute in Munich, Germany, and colleagues gave mice a drug that blocked the effects of these natural cannabinoids. Since marijuana impairs memory, they guessed that blocking cannabinoids would make it easier for mice to learn.

"But no, that is not what we saw," Lutz tells WebMD. "There was no effect on memory acquisition. We saw an effect only on processing of recalled memory. It was very surprising."

There was no difference between normal mice and cannabinoid-blocked mice in their ability to learn to fear a musical tone heard at the same time they received a painful electric shock. For a long time, the animals freeze in fear when they hear the tone. When no more shocks occur, normal mice eventually forget to fear the tone -- an important process called extinction. But without brain cannabinoids, mice never learned to forget their fear.

What makes this interesting is that extinction of fearful memories is very important to humans. It's good to respond to fear at the appropriate time -- when in combat, for example. But people with PTSD can't stop reacting to things that evoke fearful memories, even when they are in a totally safe place. People with obsessive-compulsive disorder also have extinction problems. Driven by their anxieties, they can't stop repeating the same actions over and over again.

"This study is another demonstration that extinction is a fundamental form of learning that takes place in the brain," Michael Davis, PhD, tells WebMD. We are beginning to understand this new form of learning in terms of what parts of the brain are involved and what neurochemicals are involved." Davis is professor of psychiatry and head of the Fear Collaboratory at Emory University, Atlanta.

"The implications are very exciting," Aron H. Lichtman, PhD, tells WebMD. "Perhaps there could be drugs of this sort that could be used to alleviate PTSD and other conditions." Lichtman, a researcher at Virginia Commonwealth University, Richmond, studies the effects of cannabinoids on the brain.

Would marijuana itself help people overcome fearful memories? Lutz thinks not.

"If you flood the brain with marijuana, I don't know if it would be beneficial," Lutz says. "The very important thing is if one influences the cannabinoid system, you have to do it along with psychotherapy [talk therapy]. Because you can only extinguish the memory at the time you recall it. It is good for psychotherapists to discuss with patients the aversive events they experienced. The more you do this, you extinguish this memory. So to support such a psychotherapy, you could maybe influence the extinction system by increasing cannabinoid levels."

Lutz thinks that marijuana, or even a more specific cannabinoid, would likely affect too much of the brain. He says a better idea would be to develop a drug that slows the normally rapid breakdown of cannabinoids in the brain.

"There are quite a few research groups working on this," Lichtman says. "The idea is instead of treating with marijuana, to treat with inhibitors of the enzyme that breaks down natural cannabinoids."

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