The Scientific Effects of Cannabis A Guide to the Latest Medical Science

DISCLAIMER: THIS ARTICLE IS PROVIDED FOR INFORMATION PURPOSES ONLY AND IS NOT INTENDED AS MEDICAL ADVICE, OR AS THE SUBSTITUTE FOR THE MEDICAL ADVICE OF A PHYSICIAN.

What are the effects of cannabis on your body? As the use of medicinal cannabis grows, and recreational cannabis becomes legalized in more places, we thought it was worth examining the up-to-date scientifically-researched effects of marijuana on the brain.

We’ll look at recent research into cannabis on pain, anxiety, fear, depression, hunger, stress, memory, cognition, and sensory perception. That’s right—there’s a lot going on in your brain when you smoke, vape, or consume cannabis.

Research into the effects of cannabis on the brain didn’t get underway until the swinging ‘60s. Scientists discovered a bunch of different compounds at play—far more than we can get into today—but here’s a glossary of the key players:

- THC is the main psychoactive active ingredient of marijuana. It stands for the chemical name delta-9-tetrahydrocannabinol.

- CBD is one of many other non-psychoactive ingredients of marijuana. There are more than 100 cannabinoid compounds in the cannabis genus. CBD is short for cannabidiol.

- CB receptors are a class of cell membrane receptors located throughout your body which respond to THC and CBD. The name stands for cannabinoid receptors.

- The endocannabinoid system is the name given to all of the above elements interacting together in your brain and other parts of your body.

The endocannabinoid system is spread over many different areas of your brain—which is why the effects of cannabis are so broad. Here’s a summary breakdown of the CB receptor-rich areas of your brain and how they’re commonly affected by THC, depending on the dose.

Besides your brain, you also have CB receptors in other parts of your body: the immune, gastrointestinal, and nervous systems are all hooked in. Cannabis also affects your connective tissues, gonads, and various glands and organs.

So while most people assume cannabis only affects the brain, it actually has profound effects all over your body, right down to the level of epigenetics (the activation and deactivation of your genes).

Image Source: MediPharmLabs.com

In fact, according to Health Canada, the endocannabinoid system is responsible for the healthy function of “nervous system development, immune function, inflammation, appetite, metabolism and energy… cardiovascular function, digestion, bone development and bone density, pain, reproduction, psychiatric disease, psychomotor behaviour, memory, wake/sleep cycles, and the regulation of stress and emotional state/mood.”

What does this all mean for you when you smoke or vape your herb? That’s what we want to unpack today. And there’s a lot to unpack. 

The scientific research into the chemical action of THC on animals—usually mice and rats—is well underway. Human trials are less forthcoming, but we’re getting there. 

As of 2020, a search of the scientific literature for the term cannabinoid returns more than 100,000 articles. So let’s take a look at some of the most hard-hitting evidence gathered so far, which focuses on its potential medical applications.

Pain is your body’s way of telling you something is wrong with your body. Whether it’s caused by an accident or illness, it’s the most common reason people seek medical aid. But because pain has many causes, it can be difficult to treat. Certain types of pain are untreatable with our existing medical stash, and if they are, the drugs come with debilitating side effects.

Post-surgical pain is one example. Opioids are associated with nausea and vomiting, which is not what you want when you’ve just had part of your bowel removed. By contrast, cannabis can reduce pain while providing anti-nausea effects at the same time.

Cannabinoids have shown significant promise in experiments on pain. Peripheral pain-detecting nerves contain abundant cannabinoid receptors, and cannabis has been shown to block peripheral nerve pain in animal studies. Mack & Joy (2000) explain the use of marijuana for pain and its potential applications for people suffering from AIDS, cancer, and other causes of chronic and hard-to-treat pain.

Fear and anxiety often occur at the same time, but they’re not interchangeable. 

It’s all about context. Fear comes from the perception of a threat that’s real and you clearly understand—like an angry bear charging towards you. Anxiety arises from an unknown or vague sense of threat—like the thought of going camping in angry-bear-infested woods.

When it comes to cannabis and anxiety, the dosage can create a paradox. In rodents, low doses of cannabinoids (1μg/kg) had anti-anxiety effects, while much higher doses (50μg/kg) increased anxiety (Rey et al., 2012). The explanation for this lies in the complex interplay of THC and GABA (a neurotransmitter) affecting transmission and suppression at receptors in the brain.

Cannabis has similar paradoxical effects on classical fear conditioning in mice (Metna-Laurent et al., 2012). Low doses of cannabis improved active coping behavior, while higher doses reduced coping behaviour and promoted freezing. 

The upshot is that, in the future, dose-appropriate cannabis may provide therapeutic relief to people suffering from anxiety-related illnesses—including generalized anxiety disorder, depression, obsessive compulsive disorder and post-traumatic stress disorder.

Major depressive disorder is estimated to affect 7% of all adults in the US (over 17 million people) where the most popular drug treatments are SSRIs. But SSRIs in their many analogues are notoriously unreliable—and come with a host of negative side effects, such as an increase in suicidal tendencies on first use, and long term sexual dysfunction.

Low doses of cannabis have been proven to create anti-depressant effects by stimulating the serotonergic system (Bambico et al., 2007). Another study found high doses (3mg/kg) in mice also created anti-depressant effects, but via a different route: the catecholaminergic system (Häring et al., 2013). 

The early evidence in animal studies suggests potential for using low doses of cannabis for depression in humans, and with fewer side effects than existing drugs.

What’s the difference between hunger and a strong appetite? Hunger is a physical sensation—a pain in the lower chest, contractions of the stomach, and a feeling of weakness—causing a physical drive to eat. It’s driven by the interaction of hormones in your body. Meanwhile, appetite is all psychological. It’s affected by habits, culture, taste, and other mental factors.

Marijuana is well known to produce the munchies and it does this by creating physiological hunger. But it turns out that, like anxiety, cannabis has a biphasic effect on food intake too. 

Mouse studies found that low doses of THC (1mg/kg) promoted hunger, while high doses (2.5mg/kg) actually reduced hunger (Bellocchio et al., 2010). 

The therapeutic application for this may one day extend to people suffering from the serious health effects of obesity—provided the benefits outweigh the downside of the cognitive impairment produced by a high-dose treatment.

Stress is a feeling of emotional or physical tension. It can come from any event or thought that makes you feel frustrated, angry, or nervous. It’s your body's reaction to a challenge or demand, and it evolved to help you cope in the face of suspected danger. But when you’re unable to change the circumstances causing your stress, the reaction can become worse than the original problem. When stress gets out of control like this, it becomes chronic.

Your endocannabinoid system generally inhibits stress, and recent data shows that chronic exposure to stress dysregulates this system (Hillard et al., 2014). The use of cannabis to reduce stress in the long term, by helping the endocannabinoid system to stay regulated, is supported by reports from experienced cannabis users of calmness and reduced anxiety. 

Animal studies found that early life stress profoundly alters the endocannabinoid system and increases vulnerability to psychological conditions in later life (Llorente-Berzal et al., 2011). In men, such psychopathologies tend toward substance abuse, antisocial personality and attention deficit disorder; while in women, chronic stress induces higher rates of depression, anxiety and eating disorders (Palanza, 2001).

As a result, medicinal cannabis could one day have widespread beneficial health impacts, by regulating your endocannabinoid system and countering stress at its root.

In its simplest form, sensory perception is a two-step process. First, you sense your environment physically (where the main senses are sight, sound, touch, taste and smell). Second, your brain processes these sensory signals to make meaning from them.

For instance, light reflecting from the ocean stimulates your eyes. This stimulus is transformed into neurogenic energy, which is sent to your brain for interpretation. And now you see the light.

Cannabis has profound effects on your sensation of your body and motion. Like all mammals, you have CB receptors in the basal ganglia of your brain which mediate movement. One mouse study found that the activation of the CB receptors in the basal ganglia created hypersynchrony—greater synchronization of chatter between neurons—which may explain the sensory high associated with marijuana (Sales-Carbonell et al., 2013).

Now widely marketed as having therapeutic effects on the brain, CBD—a non-psychoactive component of marijuana—has been proven in experimental models to show anti-inflammatory and antioxidant effects, among others. We may see its future use as a treatment for neuroinflammation, oxidative injury, nausea, vomiting, anxiety, and schizophrenia Fernandez-Ruiz et al. (2013). 

Researchers also point to the use of CBD in clinical trials for Huntington’s disease, for which treatment options are extremely limited, as well as the proven action of CBD on serotonin and adenosine receptors in the brain. There are hints that it may be used to kill cancer cells, as indicated in a study by Shrivastava et al. (2011) of breast cancer. 

However, clinical trials of CBD are still in their infancy, causing some debate among scientists. One literature review by Sholler et al. (2020) cited clear evidence to support the use of CBD for epilepsy, but claimed mixed results or inappropriate methodology for treating anxiety, pain, inflammation, schizophrenia, substance-abuse disorders, and post-traumatic stress disorder.

Currently, CBD derived from hemp is widely legal, while the higher-yielding CBD from marijuana has tighter restrictions. It is sold under various product labels and touted to induce sensations of relaxation, happiness, pain-reduction, stress-relief, and sleepiness, although the evidence supporting this may be somewhat cherry-picked for lack of better data.

The use of cannabis has been wrapped in stigma for decades, despite its broad therapeutic potential compared to more socially-accepted drugs like alcohol, caffeine, and nicotine. It has myriad effects on the brain and body, thanks to the nature of the endocannabinoid system, and animal studies demonstrate compelling therapeutic effects on anxiety, stress, and depression.

Science will continue to drive our understanding of the brain on cannabis. Politics permitting, as we generate more data from human studies, we could well see cannabis being prescribed for a range of psychological and medical therapies in future.

This article is based on the scientific research detailed in the book Cannabinoids by Vincenzo Di Marzo, available for free at the Wiley Online Library.