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Can Cannabis Help Mental Illness? – De-Natured

December 15, 2019

On Nature League, we spend the third week
of each month exploring a current trending article from the peer-reviewed literature. Scientific information isn’t just for scientists-
it’s for everyone! It just requires a bit of a break down. [CHEERY INTRO MUSIC] For this month’s De-Natured segment, we’re
going to look at an article released in August 2018 in the Journal of the American Medical
Association Psychiatry. This month is all about plants, and in this
month’s Lesson Plan we began by mentioning that most organisms on Earth depend on plants
to live. Not only do plants provide oxygen to the atmosphere,
but they serve as the energy starting point for many living food webs. But in the realm of human medicine, plants
and their isolated compounds can yield much more than oxygen and food- especially in the
case of cannabis. In this paper entitled, “Effect of Cannabidiol
on Medial Temporal, Midbrain, and Striatal Dysfunction in People at Clinical High Risk
of Psychosis”, the researchers report the results of a new clinical trial that investigated
how cannabidiol, or CBD, can affect individuals at high risk of psychosis. So here’s what’s already known. Cannabis is a genus of flowering plants- plants
that have been used by humans for thousands of years for a multitude of purposes. Two well-known varieties of plants in this
genus are commonly known as hemp and marijuana. Two chemical compounds have contributed to
the well-known nature of Cannabis plants. The first is cannabidiol, or CBD, and it’s
primarily found in hemp. The second compound is tetrahydrocannabinol,
or THC, and it’s primarily found in marijuana. While both compounds have the exact same molecular
formula, THC is psychoactive, meaning it can create a high, or euphoria. But what do cannabis plants have to do with
psychiatry? That’s where brain chemistry comes in. The reason our bodies react to CBD and THC
at all has to do with the fact that human brains have an endocannabinoid system. Alterations in this system are associated
with the symptom of psychosis, which can be generally defined as a loss of contact with
reality. While some research has shown that regular
cannabis use can be a risk factor for developing psychosis, especially in teenagers, these
findings specifically refer to THC. The other compound, CBD, can actually have
the opposite effect. In fact, some clinical studies have shown
that CBD has antipsychotic properties for people with certain mental disorders. Despite a growing body of evidence that CBD
can be beneficial to those suffering psychotic symptoms, scientists have yet to figure out
how. To address this, the research team observed
the effects of CBD on three specific regions of the brain in people at clinical high risk
of psychosis. The first of these regions is the medial temporal
lobe, or MTL, and its primary function has to do with new learning. The other regions are the midbrain and striatum,
which also contribute to learning in the form of helping to encode and update information
in our memory. To observe the effect of CBD on the brain,
the team had participants perform something called the verbal paired associate learning
task, or VPA. Participants at clinical high risk of psychosis,
referred to as CHR, were recruited as well as healthy control participants who were not
at CHR. For the purposes of this video, we’ll refer
to CHR participants as high risk participants to get away from being too bogged down in
initializations. In the study, high risk participants were randomly
assigned to a CBD treatment or placebo treatment. After taking the assigned drug, participants
performed a VPA task while having their brain scanned using functional MRI. The healthy control group didn’t receive
any drug treatment, but they still did the tests and imaging. But what exactly did the VPA task entail? It actually has three separate testing conditions:
encoding, recall, and baseline. During encoding, participants answered yes or no
to whether a pair of words went well together. So for example, “sharks” and “awesome”
– definite yes! In the recall condition, participants were
shown one of the words they saw during encoding and asked to say which word it had been paired
with. The baseline bit was a control of sorts where
the participant looked at a blank version of the setup they’d seen during encoding
and recall. The response of the brain during the VPA task
was measured using fMRI. Specifically, the scan measured the blood
oxygen level-dependent, or BOLD, response of the brain. Basically, this allowed the researchers to
measure the flow and composition of blood in the brain during the encoding and recall
parts of the VPA task. Then, they could compare these responses to
the baseline results. So what did they find? Overall, high risk participants who were assigned
a placebo had several regions of the brain activate differently than people in the control
group. Similar to previous studies, these regions
included the three thought to be associated with psychosis. The specific hypothesis the team was testing
was whether participants at high risk who were given CBD would have a level of brain
activation in between the activation levels of the control group, and the high risk group
who were given placebo. The team did find this middle ground activation
in the striatum during encoding, and in the parahippocampal cortex and midbrain during
recall. These results suggest that for these specific
brain regions, CBD may help normalize brain responses in individuals at clinical high
risk of psychosis. This article was published in the one of the
most prestigious families of medical journals. In addition to academic circles, the results
have made headlines in the news as well. Here are some reasons why I think this study
is capturing both scientists and citizens. First of all, the results are directly relevant
to helping humans. Unlike some other articles that we’ve discussed
on De-Natured, this study has a direct human end use, and an important one. Mental health disorders affect people in every
walk of life, and in the case of psychosis, as many as 3 in 100 people in the U.S. will
experience the symptom of psychosis at some point in their lives. Another reason I think this study made the
cut is because the research team was the first to do something. In this case, they are the first to give evidence
of how CBD acts in the brain to reduce psychotic symptoms. This is a major level up from just knowing
that CBD can reduce these symptoms. And of course, whenever there’s a promising
discovery in the medical field, there’s the potential for profit. There is a growing body of literature supporting
the use of CBD for medicinal purposes. And that means major money for those involved
in supplying the product. In the United States alone, hemp-derived CBD
is predicted to soon become a billion dollar market, and that’s without federal legalization. There is undoubtedly a lot to gain from using
this particular plant product for medical treatments, and money is certainly part of
that gain. The devil is in the methods section when it
comes to issues in experimental design. However, this research team did a great job
of removing potentially confounding variables and removing bias where possible. For example, the study design was parallel-group,
double-blind, placebo-controlled, and randomized. Randomization allows the researchers to remove
the bias that comes from assigning specific people to specific treatments. It’s picking names out of a hat instead of, say,
because you like their asymmetrical haircut. Double blind trials are ones where the participant
and the researcher aren’t in on who was assigned which treatment. That way, the researchers are less likely
to be looking for certain associations. If a researcher knew a participant had been
given the CBD, they might start looking for some kind of result, or jump to conclusions
unintentionally. We just can’t help ourselves when it comes
to investigating things- it’s impossible to not start explaining what we see, and double-blinding
a trial is a great way to avoid that. What about the “parallel groups” bit of
the research design? This piece is actually more of a limitation
of the study. In parallel group studies, each participant
only receives one of the treatments, and then those people are compared to separate individuals
who received the other treatment. In this study, this meant that the high risk
participants either received the CBD or the placebo, but none of them were actually observed
under the effects of both. With a non-crossover design, the baseline
is a bit iffy. I mean, just think about how different we
all are when it comes to chemical reactions! Take alcohol, for example. Comparing you sober to a friend who’s had
a bit to drink might be a completely different story than if you reversed the roles. Luckily, the researchers do an awesome job
of pointing out limitations like this in the discussion section of the paper. They mention the issue of the parallel design
structure, and suggest that a study be done where each high risk participant be tested
with both the placebo and CBD treatment. That said, they mention that the two high
risk groups were reasonably similar in terms of demographics and baseline health measures. This does, however, lead me to another critique
of the study, and that is the sample pool of participants. One potential problem area has to do with
sample size. There were 15 high risk participants assigned
CBD, 16 high risk participants assigned the placebo, and 19 age matched healthy controls. While these numbers do allow for testing statistical
significance at the cutoff levels the team was interested in, more is almost always better
when it comes to determining the strength of an effect. There’s also the issue of diversity. In the table showing sociodemographic measures,
the paper only reports age, sex, and education level. However, there’s no mention of variables
like race and ethnicity, meaning that this could be yet another psychiatry study done
on a Caucasian sample. Conducting research on participants of varied
backgrounds is essential to understanding the full picture of drug-brain interactions. Here’s the thing. Humans and non-human animals have been using
plants for medicinal purposes throughout the history of their time on Earth. Understanding how the chemicals in certain
plants can affect our brains is a really complicated area of research, and a study like this one
is just a single piece of that journey. As the research team put it themselves, this
wasn’t so much of a clinical study as it was a proof of concept, pilot study. It’s exciting to imagine what we might find
next when it comes to this amazing kingdom of life on Earth. Thanks for watching this episode of De-Natured
here on Nature League. Nature League is a Complexly production: head
over to our sister channel SciShow Psych if you’d like to learn more about the complicated
and amazing nature of the human brain.

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