In case you haven't noticed, marijuana stocks are absolutely on fire. Many of the largest pot stocks by market cap have seen their valuations double, triple, or perhaps head even higher over the trailing 12 months.

At the heart of this surge is a rapid and decisive change in the way the public thinks about marijuana. Gallup, which for nearly 48 years now has kept tabs on consumers' opinions about pot, found in October 2016 that 60% of its respondents favored the idea of legalizing recreational weed. Comparatively, only a quarter of respondents felt the same way back in 1995, the year before California became the first state to legalize medical cannabis.  The result of this shift in perception has been an increase in legal sales growth of around 30% annually in the United States, depending on your source.

A street sign that reads "risk ahead."

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However, just because the legal-weed industry is on fire, it doesn't mean every marijuana stock is therefore a good investment opportunity. In fact, some pot stocks are living life dangerously and could find themselves in big trouble if the cards don't fall their way. Marijuana stocks are already inherently risky given that it's an illegal substance in the U.S. and a vast majority of global countries, but these three pot stocks bring that risk to an entirely new level.

Zynerba Pharmaceuticals

Shareholders in clinical-stage cannabinoid-based drug developer Zynerba Pharmaceuticals (ZYNE) learned all too well recently that this is a company that likes to live on the edge. Having produced no genuine efficacy data before August, Zynerba has since released data from three midstage studies involving its lead drug ZYN002, a cannabidiol (CBD)-based gel. This gel and ZYN001, which is just getting into early stage studies, are Zynerba's only clinical products.

The results from Zynerba's three trials were very mixed. The Star 1 study in patients with epilepsy missed the mark by a mile. Of the two doses tested, neither reached statistical significance in terms of a median reduction in focal seizures, and the low-dose outperformed the high-dose, which is the opposite of what we'd have expected.

In the Stop study in patients with osteoarthritis (OA) of the knee, ZYN002 missed the primary endpoint once again but did wind up hitting a handful of secondary endpoints. These secondary endpoint were enough for management to opine that moving ZYN002 forward for OA of the knee makes sense.

A doctor holding a cannabis leaf between his hands.

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Most recently, ZYN002 rocked in the Fab-C trial for patients with Fragile X syndrome. It led to a clinically meaningful improvement of 46% in the total score of Anxiety, Depression, and Mood Scale (ADAMS) at week 12 compared with baseline, as well as improvements in all measures of the Aberrant Behavior Checklist for Fragile X.

With ZYN001 still a ways away from producing meaningful clinical data, shareholders are left with one failed study, one reasonably good study, and one advancing study that's a dice-roll at best. Investing in Zynerba is certainly living life dangerously.

Axim Biotechnologies

Another marijuana stock bound to take investors on something of a roller-coaster ride is clinical-stage cannabinoid-based drug developer Axim Biotechnologies (AXIM -33.33%). Axim has 16 (yes, 16!) clinical studies listed in its product portfolio on its website, although just a handful have moved into actual clinical-stage trials. The remainder are in pre-clinical testing and conceptualization. 

Though Axim has a number of intriguing ideas on paper, including chewing gums that control-release cannabinoids to treat various diseases including irritable bowel syndrome, pain spasticity associated with multiple sclerosis, and restless leg syndrome, funding is the real concern.

A man emptying his piggy bank and finding very little money.

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The company ended the second quarter with $4.1 million in cash. However, as noted, it wants to run 16 clinical-stage trials, and in a perfect world move those trials through three stages of testing, and then pay for the drug application and marketing of these products. $4 million in cash simply isn't going to cut it, leaving the potential for Axim to significantly dilute investors in the future with share offerings to raise cash.

Just as worrisome, Axim's $4.33 million in current assets is less than the $4.93 million in claims in total current liabilities. In other words, it may not have enough cash on hand to cover its expenses over the next year. If we include long-term liabilities as well, Axim has a $3.43 million deficit. That's not good at all.

But the most troubling aspect of the company is that it's worth $421 million without having produced much in the way of clinical efficacy. As noted, most of its studies are still in the preclinical stages. Investors appear to be taking big risks by placing their bets on Axim.

Corbus Pharmaceuticals

Last, but not least, Corbus Pharmaceuticals (CRBP 0.96%) is proving to investors that it likes to live life dangerously. Though the clinical-stage developer of synthetic oral endocannabinoid-mimetic drugs has four ongoing clinical studies covering systemic sclerosis, dermatomyositis, systemic lupus erythematosus, and cystic fibrosis (the latter being most important), it has just one drug in development. That's right, folks; it's anabasum or bust.

A doctor holding a bag of cannabis buds in one hand and cannabis-infused capsules in the other.

Image source: Getty Images.

Anabasum is designed to bind with naturally occurring CB2 receptors expressed on immune cells and fibroblasts. This focus on the cannabinoid receptor system is why Corbus is often lumped in with "marijuana stocks." What makes anabasum so intriguing, especially in cystic fibrosis (CF), is that it's being targeted as a general anti-inflammatory. In other words, it would be possible, if approved, to use anabasum in all CF patients and not just one's with specific genetic mutations. That's why anabasum's patient pool could be considerably larger than your typical CF drug.

Now here's where things get tricky. The company's phase 2 in CF demonstrated a 75% reduction in the pulmonary exacerbation event rate compared to the placebo with the 20 mg anabasum dose. But, and this is a big but, the study also showed no statistical improvement in CF patients' forced expiratory volume in the first second, known as FEV1. Successful CF drugs usually deliver a significant improvement in this measure of lung function, and anabasum did not. 

With a lot of Corbus' valuation riding on its CF study, one wrong move could mean bad news for investors.