LONDON, Ont. -- Some London researchers are working on building a better bud. They aim to take what's learned in the lab to create medical marijuana substitutes that pack health benefits without leaving users bouncing between paranoia and listlessness.

Western University professor Steven Laviolette and his partners are looking for investors for their start-up biotech company, Indica Agrifarm. (Indica is a variety of marijuana plant.)

"We're excited about it," Laviolette said.

It was 13 years ago Health Canada began to regulate the use of marijuana prescribed by doctors.

But earlier this year it became big business when the agency ended basement operations and required medicinal pot be produced by government-licensed facilities.

The changing business model is expected to lead to a spike in demand: Health Canada predicts the number of users could grow from 38,000 last year to as many as 450,000 in 2024.

Marijuana contains at least 70 chemical compounds, so there's much to learn about how each affects users, Laviolette said.

That learning curve received a boost Tuesday when the scientists published their latest findings online in the Journal of Neuroscience. Using chemicals meant to simulate the effects of marijuana, they found how small doses can cause paranoia in rats, and long-term exposure can result in emotionally blunted behaviour, or what some call the "stoner" phenomenon.

The key to both reactions is an area of the brain behind the forehead, the prefrontal cortex, used for emotions and thinking, and the role played by a neurotransmitter called dopamine, which affects how people experience emotions.

The chemical used to simulate marijuana either ramped up or shut down dopamine neurons.

But those affects can be minimized in the lab: Rats given an anti-psychotic medication first didn't suffer affects that in people cause paranoia.

Use of another type of chemical blocked the reaction associated with the stoner phenomenon.

"This has huge implications for identifying potential pharmacological means to prevent some of the undesired side-effects of marijuana," Laviolette said.

jonathan.sher@sunmedia.ca