Let’s start with a clarification. While the headline does include the words “Alzheimer’s” and “marijuana,” this isn’t the story of a miracle cure for Alzheimer’s disease based on smoking pot or consuming cannabis. Instead, this is a shallow dive into what is becoming an increasingly deep subject: the growing understanding of the human body’s natural endocannabinoid system and its role in both physical and mental health.
Does The Body Really Produce Natural Marijuana?
In the late 1980s, researchers confirmed the existence of the human endocannabinoid system. Insights into the system’s role in human health began several years later when cannabis research pioneer Raphael Mechoulam identified specific cannabinoid receptors known as CB1 and CB2. It turns out that these two receptors play a key role in regulating everything from memory, mood, appetite, and metabolism to sleep, pain, thermoregulation, and immunity — and they are activated by cannabinoid compounds similar to those found in marijuana.
Mechoulam once stated:
The endocannabinoid system is involved in essentially all human disease. This is a strong statement, but it is essentially correct.
The popular press has since coined the term “natural marijuana” when describing the workings of the endocannabinoid system. A 2004 article in Scientific American magazine began with the claim:
Research into natural chemicals that mimic marijuana’s effects in the brain could help to explain — and suggest treatments for — pain, anxiety, eating disorders, phobias, and other conditions.
Research on the endocannabinoid system resulted in an increasing focus on the role of the body’s “natural marijuana” on mental function. In 2013, Mechoulam wrote:
Recently, numerous endocannabinoid-like compounds have been identified in the brain. Only a few have been investigated for their CNS activity, and future investigations on their action may throw light on a wide spectrum of brain functions.
That same year, a Stanford University-led research team shed new light on the subject of brain chemistry and Alzheimer’s disease with a study that identified early-onset symptoms of the disease and implicated a specific protein fragment known as beta-amyloid (a.k.a., A-beta) as a cause.
As the National Institute on Aging explains:
In the Alzheimer’s brain, abnormal levels of beta-amyloid clump together to form plaques that collect between neurons and disrupt cell function.
The Stanford group demonstrated that the progression toward Alzheimer’s disease actually begins well before these clumps begin to appear. A university press release reports:
Scientists at the Stanford University School of Medicine have shown how beta-amyloid, strongly implicated in Alzheimer’s disease, begins destroying synapses before it clumps into plaques that lead to nerve cell death.
A year later, the Stanford group released the results of an even more newsworthy finding. Their work indicated that the memory disruptions associated with A-beta were caused by a suppression of the brain’s endocannabinoid system.
Understanding the Stanford Marijuana/Alzheimer’s Study
Post-grad biochem students may appreciate the headline of the Stanford study, which asserts that “β-Amyloid inhibits E-S potentiation through suppression of cannabinoid receptor 1-dependent synaptic disinhibition.” The rest of us won’t get much from that statement and are also unlikely to take away much from the study summary, which explains:
β-amyloid peptide more potently blocks the potentiation of excitatory postsynaptic potential (EPSP)-spike coupling (E-S potentiation). This occurs, not by direct effect on excitatory synapses or postsynaptic neurons, but rather through an indirect mechanism: reduction of endocannabinoid-mediated peritetanic disinhibition.
Fortunately, Stanford Medical followed up with a press release that puts these findings in simpler terms.
The research team’s specific research focus was on A-beta’s effects on the hippocampus. The study’s lead author, Dr. Daniel Madison, explains:
The hippocampus tells us where we are in space at any given time. It also processes new experiences so that our memories of them can be stored in other parts of the brain. It’s the filing secretary, not the filing cabinet.
He then goes on to detail the molecular process involved in the creation of memories, which can be summarized like this:
* The hippocampus is filled with special types of nerve cells known as pyramidal neurons, which process incoming sensory information (sights, sounds, tastes, touch, and so forth), and pass it along to form memories.
* Most of the time, these pyramidal cells operate at a low level, ignoring a majority of the “beeps and burps from upstream nerve cells” generated by routine incoming sensory information – much like you might ignore soft background music.
* Nerve cells known as interneurons create a “wet blanket” effect that encourages pyramidal cells to turn down the volume and ignore this background music. That’s why we rarely remember the routine sights and sounds of the everyday.
* When there is a spike in sensory input such as pain, excitement, fear, or an unusual experience, the pyramidal cells go into overdrive. This phenomenon, which neuroscientists call plasticity, is thought to be the basis for learning and memory.
* When pyramidal cells go into overdrive, they send a message to the volume-dampening interneurons, effectively saying “hold off, this is important and I need to listen.”
* Pyramidal cells accomplish this by secreting bursts of endocannabinoids which bind to specialized receptors on the interneurons.
According to Dr. Madison:
[Pyramidal cell] plasticity ensures that volleys of high-intensity input — such as might accompany falling into a hole, burning one’s finger with a match, suddenly remembering where you buried the treasure or learning for the first time how to spell “cat” — are firmly stored in the brain’s memory vaults and more accessible to retrieval.
Unexpected Role of Cannabis-Related Compounds in Alzheimer’s
Small amounts of A-beta are found in healthy brains, and one of the unexpected findings from the Stanford team’s research was that under normal conditions, A-beta plays a beneficial role by helping moderate pyramidal cell plasticity. In other words, they are part of the “wet blanket” effect mentioned earlier.
Dr. Madison describes this process as “the molecular equivalent of yawning, eye-rolling and suggestions that this or that chatter is really not worth repeating to the world at large, so why not just shut up.”
What the Stanford team discovered was that when A-beta levels are out of balance, the brain’s endocannabinoid receptors are rendered powerless to overcome this molecular yawning and eye-rolling. And when A-beta stops endocannabinoid receptors from turning up the volume, pyramidal cells miss important messages and are unable to pass along memory-creating information.
This research study didn’t identify the exact molecular mechanism of A-beta’s disruptive actions, but they did discover that it involves an interference with the signaling process rather than blocking endocannabinoids from reaching and binding to their interneuron receptors.
Future research may pin down the details of A-beta’s disruptive effect on the body’s natural marijuana. This could in turn pave the way for new treatments for the learning impairment and memory loss associated with Alzheimer’s disease.
CannaMD is committed to bringing you news and insights on medical research related to cannabis-based therapies. We have previously reported on the potential benefits of marijuana as a therapeutic agent for relieving the symptoms of dementia, and will continue to provide updates as new research becomes available.