Premature claims of a cannabis addiction 'cure'

Tuesday October 15 2013

“Have scientists found a ‘cure’ for marijuana addiction? New treatment blocks the kick that users get from the drug,” reports the Mail Online.

Based on the evidence presented in the study, which involved animals, the answer to the Mail’s question is 'not yet'.

The study found that increasing the levels of a naturally occurring chemical, called KYNA, using a compound called Ro 61-8048 blocked the effects of the active ingredient in cannabis, THC, on the brain’s reward system which produces the pleasurable feelings associated with the drug.

The study involved rats and squirrel monkeys who were given free access to a synthetic form of cannabis. Treatment with Ro 61-8048, led to a drop-off in drug use.

Also animals that had been previously weaned off THC use were less likely to ‘relapse’ if treated with Ro 61-8048.

Side effects of Ro 61-8048, at least in animals, appeared to be minimal.

While these results are promising, further studies are required to ensure that a similar compound is safe and effective in humans.

Where did the story come from?

The study was carried out by researchers from the US National Institute on Drug Abuse (NIDA), the University of Maryland and Harvard Medical School; and the University of Caligari, and Consiglio Nazionale delle Ricerche, Italy and INSERM, France.

It was funded by the NIDA, National Institutes of Health and Department of Health and Human Services; by the Italian Ministry of Education, Universities and Research, and the University of Maryland.

The study was published in the peer-reviewed journal Nature Neuroscience.

The research was mostly well-covered in the Mail Online, though its choice of headline was unhelpful and misleading. A study involving monkeys and rats does not, however promising the results, equate to a ‘cure’ in humans.

What kind of research was this?

This was an animal study that aimed to determine whether the researchers could reduce cannabinoid use (the active chemical substances contained in cannabis) and prevent relapse by blocking the reward system in the brain activated by cannabinoid use by increasing the levels of a naturally occurring chemical.

This is the ideal study design to investigate this sort of question. However, further studies will be required to see if the findings translate into humans, and to ensure that any arising treatment is both effective and safe.

What did the research involve?

The researchers investigated whether increasing the levels of a naturally occurring chemical in the brain, called kynurenic acid (KYNA) could reduce cannabinoid use and prevent relapse.

KYNA changes the shape of a receptor (receptors are molecules found on the surfaces of cells) involved in modulating the effects of the psychoactive ingredient of cannabis (THC).

The researchers increased the levels of KYNA by inhibiting the activity of an enzyme called KMO using a compound which the researchers termed Ro 61-8048.

The researchers first confirmed that Ro 61-8048 increased the levels of KYNA in the brains of rats and reduced the levels of dopamine (the chemical involved in the reward system in the brain) induced by THC or a synthetic cannabinoid called WIN 55,212-2 in rats. They then examined the effects of Ro 61-8048 on:

  • the self-administration of WIN 55,212-2 in rats, and the self-administration of THC in squirrel monkeys, and whether this effect is specific or whether there is any effect on food intake
  • relapse’ in ‘abstinent’ animals who had previously self-administered drugs, after they were exposed to priming injections of drugs or cues associated with drug availability
  • on working memory in rats and squirrel monkeys

What were the basic results?

The researchers found that Ro 61-8048 increased the levels of KYNA in two brain regions associated with the rewarding effect of cannabinoids (the nucleus accumbens shell and the ventral tegmental area) in rats. Ro 61-8048 alone did not affect dopamine levels in the brain, but pre-treatment (giving the drug before the animals were treated with THC or WIN 55,212-2) with Ro 61-8048 prevented the increase in dopamine levels normally seen after THC or WIN 55,212-2 administration.

Pre-treatment of rats with Ro 61-8048 reduced the self-administration of WIN 55,212-2. Rats weaned off cannabinoids can ‘relapse’ if given a priming injection of WIN 55,212-2. Relapse was prevented in rats pre-treated with Ro 61-8048.

Similar results were seen in squirrel monkeys. Pre-treatment of squirrel monkeys with Ro 61-8048 reduced the self-administration of THC. However, Ro 61-8048 pre-treatment did not affect self-administration of food. Like rats, ‘abstinent’ squirrel monkeys who had previously self-administered THC can ‘relapse’ if given a priming injection of THC. Relapse was prevented in squirrel monkeys pre-treated with Ro 61-8048. Drug availability was often associated with a cue, for example a green light. Ro 61-8048 pre-treatment also prevented relapse caused by re-exposure to THC-associated cues.

The researchers then confirmed that Ro 61-8048 had no effect on memory in rats or squirrel monkeys.  

How did the researchers interpret the results?

“The present results indicate that pharmacological modulation of brain KYNA levels by KMO inhibitors could provide an effective approach for the treatment of marijuana [cannabis] dependence".

Conclusion

This study has opened the possibility of the availability of a drug that could assist in the treatment of cannabis (marijuana) dependence.

In this study, Ro 61-8048, a KMO inhibitor, increased the levels of KYNA, a naturally occurring chemical in the brain. Ro 61-8048 administration selectively blocked the effects of cannabinoids on the brain's reward system. It also prevented the ability of cannabinoids and cannabinoid-related cues to trigger relapse in rats and monkeys. 

This study is valuable for understanding the biological response of animals following the administration of drugs. However, it is not known whether the findings will definitely apply to humans. Further studies will be required to see if the findings translate into humans, and most importantly to ensure that any arising treatment is safe.

If you have a problem with drugs, there's a wide range of services that can help.

Some of these services are provided by the NHS, and some are specialist drug facilities run by charities and private organisations. You can use the service search to find your nearest NHS drug addiction support services.

You can also call the Frank helpline on 0800 77 66 00 for more information about drugs and the different options available for help and support. The confidential helpline is open every day, 24 hours a day.

Analysis by Bazian
Edited by NHS Choices