The THC in cannabis may alter the brain's susceptibility to other drugs.© Getty

Neuroscientists have found that rats are more likely to get hooked on heroin if they have previously been given cannabis. The studies suggest a biological mechanism — at least in rats — for the much-publicized effect of cannabis as a 'gateway' to harder drugs.

The discovery hints that the brain system that produces pleasurable sensations when exposed to heroin may be 'primed' by earlier exposure to cannabis, say researchers at the Karolinska Institute in Stockholm, Sweden, who carried out the study.

There has long been a debate about whether exposure to drugs such as nicotine or marijuana might lead to harder habits. Many argue that the most important factors in the equation are social ones: people who get one drug from a dealer are probably more inclined to try another. But researchers are still interested to know whether there is any physiological effect that might additionally predispose users of so-called soft drugs to harder-drug addiction.

To rule out social factors, the researchers turned to an animal model. They dosed some rats with the active ingredient of cannabis and others with a neutral compound during their adolescence (when they were about four to six weeks old). After that, they gave the rats intermittent access to heroin for several weeks, obtained by pressing a lever.

Although all rats helped themselves to heroin, the ones given cannabis's key compound, called Δ-9-tetrahydrocannabinol (THC), during their formative years showed a greater escalation in their self-dosing during the experiment. By the end, rats that'd had cannabis in their 'teens' were pressing the lever that delivered heroin about 1.5 times more than the rats that had previously been drug-free.

The researchers report the findings in the journal Neuropsychopharmacology¹.

Hard to kick

"It's a nice study, although somewhat preliminary," comments Ian Stolerman, a psychopharmacologist at Kings College London. "It's too early to say there's a consensus, but a small number of studies like this suggest that there is a physiological basis for this effect."

The rat results may be due to the fact that both THC and heroin act on a pleasure pathway in the brain called the opioid system, explains study leader Yasmin Hurd, now at Mount Sinai School of Medicine in New York. Exposure to opiates such as heroin triggers the release of chemical messengers in the brain called opioids that stimulate pleasant sensations.

The receptor molecule to which THC binds is also found on brain cells in the opioid system, Hurd adds. Over-stimulation of these receptors through exposure to cannabis may alter these cells so that the brain either feels intensely rewarded by subsequent heroin exposure, or needs an ever-increasing dose to feel the same pleasure — both of which could lead to addiction.

If so, a similar effect may be seen with drugs such as cocaine and amphetamines, which involve another brain pathway called the dopaminergic system, Stolerman adds. Cells involved in this pathway also have THC receptors, possibly indicating that they could also be modified by cannabis exposure.

A slippery slope

But even if the gateway effect is one day found to also have a biological basis in humans, the effect is undoubtedly complicated by social factors. Some social commentators have ascribed the perceived gateway effect to the simple fact that cannabis is cheaper than many other illegal drugs, meaning that adolescents are more likely to use it before graduating to other substances.

Hurd, however, feels that softening the law against marijuana at this point would be "ridiculous", given the number of unknowns about its effects. She adds that two other drugs that also stimulate opioid cells, and could therefore also feasibly cause a gateway effect, are nicotine and alcohol. "If we turned back the clock with the knowledge we have now, these two drugs would never have been legalized," Hurd says.

The discovery also warns against complacency that cannabis does not have any lasting effect in young people who use the drug. "Lots of mothers say 'oh well, at least it's not cocaine'," Hurd says. "But this is not about the short-term effects. For adults to do it is one thing, but we have to consider the effects on children."

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Mount Sinai School of Medicine, New York

• References

  1. Ellgren M., Spano S. M.& Hurd Y. L. . Neuropsychopharmacology, . - doi:10.1038/sj.npp.1301127 (2006).