Published online 2 November 2000 | Nature | doi:10.1038/news001102-8


Highs and lows

David Adam reports on efforts to pin down cannabis' influence on asthma sufferers.

Researchers studying the action of cannabis-like molecules may have cracked why the drug performs in wildly conflicting ways in some clinical studies. Smoking marijuana can dilate human airways, so many people have suggested that it could be used to treat chest complaints, including asthma. But the drug triggers coughing fits in some asthma patients.

This is because cannabis can act in two different ways on the same airway nerves, Daniele Piomelli of the University of California, Irvine, and his colleagues now suggest. After unravelling the contrasting effects of 'cannabinoid' chemicals in rodents, the researchers say that they may have provided a framework for the development of better, more selective medicines to treat respiratory conditions in people.

People who smoke cannabis introduce the cannabinoid 'THC' (tetrahydrocannabinol) into their bodies, where it binds receptors and triggers nervous activity. Other cannabinoids, which are produced in the body and used as signal molecules, bind the same receptors. Piomelli's team studied a signal cannabinoid produced in rodents' lungs called 'anandamide'.

Anandamide, a weaker chemical cousin of THC, shot to fame in 1996 when Piomelli found compounds strongly resembling it in dark chocolate1. As well as acting in the brain (and now rodent lungs), the chemical is known to play a crucial role during the implantation of an embryo into the uterus wall.

The researchers investigated how anandamide (and by implication other cannabinoids, including THC) regulates airway tissue. The key, it seems, is how contracted the airway already is.

When the muscles are tensed, the anandamide signal can inhibit coughing brought on by an irritant -- Piomelli's group used the pungent component of chili peppers, capsaicin. If the muscles are relaxed, then anandamide sends them into spasm. The team reports its results in Nature2.

Antonio Calignano, a pharmacologist at the University of Naples, Italy, and one of Piomelli's team, says that the results help to clarify the effects that cannabinoids seem to have on marijuana smokers. Heavy or long-term smokers experience airway muscle relaxation; light or inexperienced users often suffer asthma-style attacks.

This is because the airways of long-term smokers are damaged -- and the muscles more contracted -- than in healthy people, Calignano suggests. But there are over sixty cannabinoids in marijuana, so there is still some way to go before the situation is clear, he adds.

Roger Pertwee, who studies the therapeutic potential of cannabanoids at Aberdeen University, UK, says that such contrasting cannabinoid dual action is also seen when the compounds are used to treat glycoma in the eye. Asthma is one of the major targets for possible cannabinoid therapies, he adds, but warns that possible new treatments are still some way off because so little research has yet been done. 

  • References

    1. DiTomaso, E., Beltramo, M. & Piomelli, D. Brain cannabinoids in chocolate. Nature 382, 677 - 678 2000. | Article |
    2. Caliagnano,A. et al. Bidirectional control of airway responsiveness by endogenous cannabinoids. Nature 408, 96 - 101 2000. | Article | PubMed | ChemPort |