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Can Marijuana Cure Alzheimer's Disease?

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of Aβ amyloid plaques and twisted tangles of a protein called "tau" in regions of the brain responsible for memory and cognition. Despite our growing understanding of how AD progresses, however, scientists still haven't pinpointed the exact cause of this disease. 

As a result, AD presently sports one of the worst clinical failure rates for experimental drugs of any major human disease. Punctuating this point, a recent review study revealed that a stunning 99.6% of clinical trials for AD failed to improve patient outcomes over the course of 2002 to 2012.

Image source: Getty Images.

Unfortunately, this negative trend is showing absolutely no signs of reversing course. In 2013, for instance, Pfizer (NYSE: PFE) and Johnson & Johnson (NYSE: JNJ) shuttered their anti-amyloid AD research program after the monoclonal antibody, bapineuzumab, flopped in two late-stage trials.

Since Pfizer and J&J's high-profile failure, Eli Lilly's (NYSE: LLY) amyloid-busting monoclonal antibody, solanezumab, has also flamed out in late-stage testing, and Merck's  (NYSE: MRK) BACE inhibitor, verubecestat, followed suit earlier this year as a possible treatment for patients with mild to moderate forms of the disease. 

Although neither Lilly nor Merck has totally abandoned its aspirations of potentially bringing the first disease-modifying treatment to market for AD, the cold, hard truth is that the current approach of reducing amyloid plaques in the brain has been a complete dead end thus far.

And that fact doesn't bode well for the slew of other experimental anti-amyloid treatments therapies currently under development for AD right now -- such as Biogen's (NASDAQ: BIIB) aducanumab, or Amgen (NASDAQ: AMGN) and Novartis' (NYSE: NVS) BACE1 inhibitor, CNP520 -- just to name a few. 

Why are pharmaceutical companies still pursuing Alzheimer's disease?

Amgen, Biogen, Lilly, J&J, Merck, Pfizer, and Novartis have reportedly spent billions on their respective AD clinical programs. That's a remarkable figure in light of the fact that no experimental drug has been approved for AD since 2003, and the clinical failures for this devastating neurological disorder continue to mount.

So why are these titans of the pharmaceutical and biotech landscapes plowing forth with their almost certainly fruitless AD research efforts?

The short answer is that the payoff would be immense. As Americans' sixth-leading cause of death, and over 5 million individuals presently afflicted with this disease, industry insiders have estimated that a truly disease-modifying drug could perhaps generate peak annual sales of over $20 billion within a decade. Such a monstrous sales figure would be a game changer for middleweights like Biogen or even megacap titans like J&J, Pfizer, or Novartis. 

The take-home point is that AD is by far the most valuable disease market in the pharmaceutical arena at the moment. The only problem is that none of these blue bloods of the industry have even come close to sniffing a positive late-stage result in the past 14 years or so, resulting in literally billions of dollars in wasted clinical efforts. 

Can medical cannabis provide a novel solution?

The odd twist of this story is that medical cannabis, or its derivatives such as dronabinol (a synthetic form of the active component of marijuana known as delta-9- tetrahydrocannabinol, or THC) have exhibited some extremely encouraging results in preclinical studies. 

Image source: Getty Images.

The backstory is that medical cannabis has been hypothesized to be a potent AD drug ever since a 2003 study showing that some of the support elements (neuralgia) of the central nervous system negatively impacted by the growth of amyloid plaques tend to overexpress so-called "endocannabinoid receptors."

While endocannabinoid receptors are usually involved in the regulation of appetite, emotions, and pain sensation, they have also been shown to exhibit a neuroprotective function -- leading some researchers to suggest that THC may trigger a neuroprotective response in AD patients. 

Keeping with this theme, a handful of studies have, in fact, shown that even small doses of THC can inhibit amyloid plaque growth, implying that this natural drug may be a powerful therapeutic option of patients suffering from this deadly neurodegenerative disorder.

Although the exploratory research performed so far on the latent clinical benefit of THC on AD symptoms and progression is indeed quite encouraging, a recent review study on the topic came to a somewhat less enthusiastic conclusion. 

Citing the lack of large, randomized trials likely stemming from marijuana's Schedule I status in the United States, researchers at the University of British Columbia stated that the scientific evidence supporting medical cannabis' potential therapeutic benefits in AD patients was "weak and limited" at this time. The researchers could only identify two studies -- out of a possible 393 that met their selection criteria -- that directly addressed this hypothesis in human subjects. 

What's the next step?

The long and short of it is that the pharmaceutical industry's current approach to developing a game-changing AD simply isn't working. As a matter of fact, it would be downright shocking if either Biogen's aducanumab or Amgen/Novartis' CNP520 -- two of the most closely watched experimental AD therapies right now -- proved to be viable therapies, based on the litany of failures for similar drugs in the recent past.

Nevertheless, the prohibitive government regulations surrounding medical research into cannabis are clearly hampering the industry from exploring this promising alternative. The preclinical studies to date, after all, have provided some rather compelling evidence of a therapeutic benefit of marijuana in AD patients. And normally, the industry would pounce on such findings by launching a full-fledged clinical program in human subjects. Marijuana's Schedule I status, however, has put the kibosh on this promising line of research. 

So, until the regulatory landscape for medical marijuana research becomes less restrictive, the pharma industry seems destined to keep pursuing the same lines of experimental AD therapies that have failed time and time again. And marijuana's potential clinical benefit in AD will almost certainly remain largely unexplored.  

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George Budwell owns shares of Pfizer. The Motley Fool owns shares of and recommends Johnson & Johnson. The Motley Fool recommends Biogen. The Motley Fool has a disclosure policy.