There's little question that marijuana presents a long-term growth opportunity for investors, especially as the U.S. moves toward legalizing the substance at the federal level. 

Many of the big, early players in the cannabis space, including Canopy Growth, Hexo, and Tilray, all soared quickly out of the gate only to fall back to earth as the reality of coping with the labyrinthine framework of Canada's regulatory system proved more challenging than originally expected. But there's hope the U.S. system won't fumble the ball in the same way.

Investors can still jump into the market now and make big returns. Industry analysts at New Frontier Data estimate that legal marijuana sales in the U.S. will grow at a 16% compound rate annually through 2025 to reach $43 billion -- without including the potential for new states or federal legislation. Some 64% of those sales will be for adult recreational use and the remaining 36% will be for medical patients.

Those cannabis consumers will be buying their marijuana at authorized dispensaries, and it's for that reason I think investors should look at the multi-state operator segment of the market for their greatest returns today.

Marijuana plant

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Columbia Care

"Grow quickly and get to scale" seems to be the motto Columbia Care (CCHWF -1.48%) has adopted in its bid to be a leading MSO in cannabis. Thirty-six states have legalized either recreational or medical usage of marijuana, and Columbia has 99 dispensaries in 17 of them. It also operates 31 cultivation and manufacturing facilities and offers wholesale distribution in 13 markets.

It's using acquisitions to rapidly expand its dispensary footprint, including vertically integrated medical marijuana operator Green Leaf Medical; Ohio-focused CannAscend, which operated four dispensaries; and California-based cultivator, wholesaler, and retailer Project Cannabis. That's key because Columbia's growth potential accelerates as more states approve both medical and personal cannabis use, so having a broad, available network enables it to get up and running quickly in any market.

Columbia Care says its revenue triples or quadruples when usage parameters expand, and because twice as many states currently allow medical use as those that allow recreational consumption, this MSO is positioned to capitalize as the former change into the latter.

Even if financial performance is weighed down by acquisitions in the short term, now could be a great time to buy the stock. Columbia Care's shares are down 32% year to date, but it could rapidly turn around in the near future.

Marijuana plant being examined.

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Jushi Holdings

While Jushi Holdings (JUSHF -2.19%) is also expanding its dispensary presence nationally, it is taking a far more narrow and focused approach. Currently, just three states -- Pennsylvania, Illinois, and Virginia -- account for 80% of its revenue this year, and Pennsylvania is the predominant locale, where 13 of its 20 retail outlets are located. 

That said, Jushi has a retail presence in two more states (California and Massachusetts), possesses a growing roster of branded retail stores with over a dozen more planned by the end of the year, operates five cultivation sites, and has a similar number of extraction and processing facilities, giving it a total presence in seven states so far.

Jushi's unique opportunity comes from the states it targets, which limit its competition either by placing a cap on the number of dispensary licenses they will allow or assigning them based on jurisdiction. That means Jushi won't necessarily be displaced by a deep-pocketed, late-to-the-game competitor.

With less than two dozen dispensaries and revenue forecast to reach just $255 million this year, Jushi Holdings is smaller than many of its rivals, but analysts are forecasting sales to expand exponentially, hitting nearly $1 billion by 2024. That will help catapult it to the forefront of the industry and would undoubtedly bring its stock price along for the ride.

Medical marijuana in cannister

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Trulieve Cannabis

Trulieve Cannabis (TCNNF -2.31%) is an even more concentrated player than Jushi because it is almost exclusively a Florida-based medical marijuana stock -- at least for the moment.

Trulieve is the largest of the state's licensed medical marijuana providers, with the greatest number of dispensaries and the biggest volume of sales, and it's only just now trying to replicate that success in other jurisdictions. It was recently awarded a license to operate in its seventh state (Georgia). Still, 90% of its dispensaries are in Florida.

This company, too, is trying a novel approach to expansion, having successfully launched a pilot program to sell its premium-quality cannabis clones at one of its Massachusetts dispensaries. That will allow home growers to use the genetics of Trulieve's high-quality plants to grow their own marijuana plants at home.

The first phase of the plan is limited to Trulieve's Chocolope NewBerry Sativa strain, but if well received, the cannabis company could introduce other strains and add more locations where customers can purchase them.

This gives Trulieve the opportunity to grow its business by trading on its reputation, much the way craft beer brands allow home brewers to buy kits of their favorite craft beer to make at home.

As it is also acquiring Harvest Health & Recreation, giving it access to that MSO's five-state dispensary portfolio, Trulieve could be another leading marijuana company much sooner than expected.