Your Brain On Cannabis
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Cannabis and the brain is a meaty subject. Identifying the various ways cannabis affects the brain is complicated, and we’ve only just begun to unravel many of the mysteries. Further complicating the study of cannabis consumption and its effect on the brain, is that much of the research — as well as much of what we hear — is often contradictory.

On the one hand, we’re inundated with messages that cannabis impairs a user’s cognitive function — like short-term memory. On the other hand, we read news reports on how cannabis can act as a neuroprotectant, perhaps even preventing the onset of neurodegenerative diseases, like Alzheimer’s.

How can this be? The truth is, cannabis is a diverse, complex plant comprised of hundreds of chemicals. Two of the most prominent constituents — THC and CBD — affect us in significantly different ways. THC is the main psychoactive constituent, while the largely non-psychoactive CBD can offset (or balance) many of the effects of THC. We’ll dive deeper into the differences between how THC and CBD work later in the article, but no discussion of cannabis and the brain can start without a fundamental understanding of the endocannabinoid system — the ECS.

What Is the Endocannabinoid System and Why Is It Important?

The ECS is a group of cannabinoid receptors located throughout the brain — including the central nervous system (CNS) and the peripheral nervous system (PNS) — that play a vital role in the regulation of our mood, physiology, and health. The discovery of these receptors has played a significant role not just in our understanding of cannabis, but of human biology, disease and health. Further, the ECS is involved in a number of physiological processes such as mood, memory, pain sensation, appetite.

Scientists have identified the two primary cannabinoid receptors, CB1 and CB2, discovered in 1990 and 1993 respectively.:

CB1 receptors can be found primarily in the brain and nervous system, but are also found in other organs and connective tissues. CB1 is the main receptor for THC, a phytocannabinoid (phyto meaning, “of the plant”), and its twin, anandamide, one of the body’s naturally occurring cannabinoids which THC mirrors. Activation of CB1 receptors, by THC, is responsible for cannabis’ psychoactive effects.  CB2 receptors are predominantly found in the immune system and associated structures, and are responsible for modulating cannabis’ anti-inflammatory effects. An immune response, inflammation is thought to be a significant factor in many diseases.

Cannabis contains at least 85 cannabinoids, the chemical compounds that interact with the brain’s receptors. The two cannabinoids people are most familiar with include THC and CBD.

THC, which is responsible for most of cannabis’ psychoactive effects, affects the brain by activating cannabinoid receptors, namely CB1. In the process, it keeps your neurons firing, promotes creativity, amplifies your thoughts, and keeps you focused on those thoughts — until stimuli distracts you to a tangential thought. In part, this explains why getting “high” is not conducive to studying or driving a car.

Interestingly, CBD, THC’s (largely) non-psychoactive sibling and the second most studied constituent in cannabis, shows little affinity to bind to either CB1 or CB2; instead, CBD seems to indirectly stimulate cannabinoid signaling by suppressing the enzyme that breaks down anandamide. As such, this partly explains why CBD appears to counteract some of the effects of THC, and why higher CBD concentrations result in a reduction of the intoxicating effects of THC. Like THC, CBD also plays an important role in appetite, the immune system and pain management.

Cannabis has a biphasic effect

The effects of cannabis vary by individual, and are highly dependent on dosing and form of preparation. It’s important to note that like many chemicals, cannabinoids — particularly, THC — has a biphasic effect, meaning low doses and high doses can have the opposite effects in users. This is partly why many people may feel relaxed with low doses of cannabis, and paranoid under high doses of THC. Logically, this is why most medical marijuana practitioners advise patients to start with a low dosage and gradually increase dosage as the patient determines how their body reacts. This process is known as “self-titration.”

Another way to think of the biphasic effect is as a therapeutic window. Cannabis has a narrow therapeutic range, meaning the difference between the optimal dosage that elicits the effect one desires versus a dosage that creates adverse effects, can be subtle. Take chronic pain as an example: most studies of cannabis and chronic pain report that when a patient consumes too high of a dosage, they may find their pain is exacerbated. Further complicating the issue is that THC and CBD levels — as well as THC:CBD ratios — can vary dramatically from strain to strain, so it’s important for people to be conscious of these levels as they find the most appropriate dosage to treat their condition.

The same goes for lifestyle users, who may find they have a preference for a particular strain. One strain may make them feel overly drowsy or anxious, while another may make them feel relaxed and happy. Everyone’s body chemistry is different, so how one responds to cannabis can vary dramatically.

How Cannabis Affects the Central Nervous System

Shortly after consuming cannabis in a smokable form, cannabinoids enters your bloodstream. From there, cannabinoids are transported to the central nervous system, where they activate cannabinoid receptors and affects — in varying degrees dependent on individual body chemistry and other variables such THC/CBD concentrations and ratios — the functioning of the various brain areas.  

Acting on cannabinoid receptors throughout the brain, cannabinoids can affect memory (through the hippocampus); concentration (through the cerebral cortex); perception (through the sensory portions of the cerebral cortex); and, movement (through cerebellum, globus pallidus, substantia nigra).

Ok, so how does that translate to how noticeable effects?

Low to moderate doses

Elevated mood, feelings of euphoria, and relaxation Mild reduction in coordination Sleepiness (although, higher CBD concentrations can contradict this effect) Mild disruption of cognitive function including concentration and memory  An Increase in creativity Blocking the detection of pain — why cannabis can be helpful in treating pain, particularly neuropathic pain Alleviating nausea — why cannabis can be useful for cancer patients going through chemotherapy An increase in appetite

High doses

Hallucinations varying from mild to moderate Paranoia  Anxiety Disorientation Exacerbation of pain

Studies, like one conducted by the University of Lausanne in Switzerland that monitored nearly 3,400 Americans over 25 years found that heavy, long-term (5+ years) chronic users of cannabis had poorer verbal memory in middle age than moderate users or abstainers.

Likewise, an increasing body of (mostly) preclinical research continues to emerge that suggest CBD can play a vital role in neurogenesis, neuroprotection, the prevention of schizophrenia and neurodegenerative disorders. Therefore, it would make sense that

although we can’t say conclusively, the most plausible explanation on why there seems to be so much seemingly contradictory evidence and paradoxical conclusions (i.e. cannabinoids “protect” or “impair” cognitive function). The most plausible explanation may be connected to the biphasic effect.

Zana Medical

Zana Medical