A drug which reduces the desire for marijuana and blocks its effect on the brain has been successfully tested in rats. Scientists say the findings may translate into better therapies for cannabis addiction in humans.

Rodents given a compound derived from a plant in the buttercup family lose their hankering for a synthetic version of tetrahydrocannabinol (THC) - the active compound in marijuana. The treatment also blocked a reward response in the animals' brains when they did receive synthetic THC.

In the first part of the experiment, Steven Goldberg at the National Institute on Drug Abuse in Maryland, US, and his colleagues placed rats in a cage with a lever the animals could push. Each time the rats leaned on the lever, they received a dose of the synthetic THC through a small tube running into their body.

Over a period of three weeks the rats learned to enjoy the effects of synthetic THC and frequently self-administered the drug. By comparison, rats that received saline solution did not press the lever often.

Goldberg's team then injected the rats with a compound derived from the seeds of the Delphinium brownii plant, which is in the buttercup family. The compound, known as methyllycaconitine (MLA), had a dramatic effect on the animals' behaviour.
Blocking dopamine

On the day that they received MLA they pushed the lever for synthetic THC 70% less than before. The drug did not seem to otherwise change the rats' movement and coordination, and had no other apparent side effects.

The scientists also took a close look at the effects of MLA on the rats' brains. They used a technique called microdialysis to take tiny fluid samples from a reward-signalling area of the brain known as the nucleus accumbens, which sits near the base of the head.

When rats receive synthetic THC, levels of the reward chemical dopamine normally shoot up in the nucleus accumbens - but MLA blocked the release of dopamine in this brain region.

"The increases in dopamine are virtually non-existent because of MLA," says Goldberg. He adds that MLA did not lower dopamine levels below normal amounts. This is important, says Goldberg, because it suggests that a similar therapy for humans would not interfere with normal reward signalling in the brain.

He notes that the drug Rimonobant, which makes monkeys less likely to self-administer THC, has been linked to depression in humans.

The exact mechanism by which MLA works remains a mystery. Scientists know that MLA binds to specific cell receptors in the brain called alpha-7 nicotinic receptors. They speculate that cannabis indirectly triggers these receptors, but cannot do so when the receptors are blocked by MLA.
Human potential

There is a genuine need for medications to help cannabis addicts overcome their drug problem, according to Goldberg: "About 10% of the people who experiment with it go on to heavy use and have trouble voluntarily giving it up. I think there is a proportion of the population who need ways to make them stop."

Drug-makers have recently made medications such as Chantix available to help people quit tobacco smoking. But researchers say that these drugs affect different nicotinic receptors than those triggered by THC.

And while some people have pushed Rimonobant as a possible remedy for addiction, Goldberg says that more options - such as one based on MLA - must be explored: "Each patient is different and what works in one might not work in another."