CBD and the Brain: What Does It
Do and What Is It Good For?
Article by Leafly
Cannabidiol (CBD) is one of many cannabinoid molecules produced
by Cannabis, second only to THC in abundance. These plant-derived
cannabinoids, or phytocannabinoids (phyto = plant in Greek), are characterized
by their ability to act on the cannabinoid receptors that are part of our endocannabinoid
system. While THC is the principal psychoactive component of Cannabis and
has certain medical uses, CBD stands out because it is both non-psychoactive
and displays a broad range of potential medical applications. These properties
make it especially attractive as a therapeutic agent.
Evaluating the Evidence
Perhaps the most remarkable thing about
CBD is the sheer number and variety of its potential therapeutic applications.
It is important to recognize that each application may be supported by
different levels of evidence. These range from ongoing clinical trials evaluating
its efficacy in the treatment of human disorders, to animal studies
investigating its behavioral and physiological effects, to in vitro work (test tube experiments) measuring its
pharmacological interactions and mechanisms of action. Each type of study comes
with its own strengths and weaknesses.
Clinical trials allow us to draw
conclusions about the safety and effectiveness of potential therapeutic agents
in humans, while animal studies and in vitro experiments
allow researchers to explore their biological actions in greater detail.
However, because the latter class of studies are not conducted in humans, the
results don’t always lead to the clinical application that we hope for—the
majority of drugs that start in human clinical trials never become approved.
Nonetheless, animal studies provide us with a strong foundation of biological
knowledge, and are where the initial breakthroughs in research are made.
Why Does CBD Have So Much Therapeutic Potential?
CBD is famous for the promise it holds for
treating treatment-resistant forms of childhood
epilepsy. A number of clinical trials, testing the efficacy of CBD in human
epilepsy patients, are currently underway. But there is also evidence, mainly
from animal studies and in vitro experiments, that CBD may
have neuroprotective, anti-inflammatory and analgesic (pain-relieving)
properties, and potential therapeutic value in the treatment of motivational
disorders like depression, anxiety, and addiction.
What’s the biological basis for this wide
range of potential medical uses? A key part of the answer lies in CBD’s
promiscuous pharmacology—its ability to influence a wide range of receptor systems
in the brain and body, including not only cannabinoid receptors but a host of
others.
Receptor Systems in the Brain
The brain contains large numbers of highly
specialized cells called neurons. Each neuron connects to many others through
structures called synapses. These are sites where one neuron communicates to
another by releasing chemical messengers known as neurotransmitters (Figure 1).
A neuron’s sensitivity to a specific
neurotransmitter depends on whether or not it contains a receptor that “fits”
that transmitter, like an electrical socket fits a plug. If a neuron contains
receptors that match a particular neurotransmitter, then it can respond
directly to that transmitter. Otherwise, it generally can’t. All neurons
contain multiple neurotransmitter receptors, allowing them to respond to some
neurotransmitters but not others.
Figure 1. Neurons Communicate Using
NeurotransmittersRight: The brain contains a huge a number of brain cells (neurons). Each neuron, represented here as a hexagon, is connected to many others. Left: The synapse is the site where two neurons communicate with each other. The “sender neuron” releases chemical signals called neurotransmitters, which stimulate receptors on the “receiver neuron.” There are many different receptor types in the brain, each one sensitive to different neurotransmitters.
Brain receptors are not only sensitive to
neurotransmitters produced naturally within the brain, like dopamine or
serotonin, but also chemical messengers produced outside the body, such as
plant cannabinoids like THC or CBD. So when you ingest an edible or inhale some
vapor, you’re allowing compounds originally produced by a plant to enter your
body, travel through your bloodstream, and enter your brain. Once they arrive,
these plant-derived compounds can influence brain activity by interacting with
receptors on neurons. But they don’t interact with all neurons, just the ones
that have the appropriate receptors.
CBD Influences Many Different Receptor Systems
Although it is a cannabinoid, CBD does not
directly interact with the two classical cannabinoid receptors (CB1 and CB2).
Instead, it affects signaling through CB1 and CB2 receptors indirectly.
This partly explains why, in contrast to THC, CBD is non-intoxicating. In
addition to its indirect influence on the CB1 and CB2 receptors, CBD can
increase levels of the body’s own naturally-produced cannabinoids (known as
endocannabinoids) by inhibiting the enzymes that break them down.
Even more intriguing: CBD also influences
many non-cannabinoid receptor systems in the brain, interacting with receptors
sensitive to a variety of drugs and neurotransmitters (Figure 2). These include
opioid receptors, known for their role in pain regulation. Opioid receptors are
the key targets of pharmaceutical pain killers and drugs of abuse such as
morphine, heroin, and fentanyl. CBD can
also interact with dopamine receptors, which play a crucial role in regulating
many aspects of behavior and cognition, including motivation and reward-seeking
behavior.
This raises the intriguing possibility
that CBD’s ability to influence either opioid or dopamine receptors may
underlie its ability to dampen drug cravings and withdrawal symptoms, effects directly
relevant to the treatment of addiction. However, we can’t say for sure at this
point; more research on CBD’s interactions with the opioid and dopamine
receptor systems is still needed.
CBD’s therapeutic potential with respect
to addiction also extends to the serotonin system. Animal studies have
demonstrated that CBD directly activates multiple serotonin receptors in the
brain. These interactions have been implicated in its ability to reduce
drug-seeking behavior. CBD’s influence on the serotonin system may also account
in part for its anti-anxiety properties, which have been robustly demonstrated
across both human and animal studies.
CBD and the Serotonin System: Exciting Possibilities
CBD’s ability to target a specific
serotonin receptor, the serotonin 1A receptor, is associated with a remarkable
range of therapeutic possibilities. Professor Roger Pertwee, a pharmacologist
from the University of Aberdeen, spoke with Leafly about this aspect of CBD
biology.
“It’s apparent ability to enhance the
activation of serotonin 1A receptors supports the possibility that it could be
used to ameliorate disorders that include: opioid dependence, neuropathic pain,
depression and anxiety disorders, nausea and vomiting (e.g. from chemotherapy),
and negative symptoms of schizophrenia,” he said. “One big unanswered
question is what the human clinical relevance and importance of each of these
potential therapeutic uses of CBD, identified solely by examining data from
non-human preclinical research, actually is.”
Given that these possibilities come mainly
from animal studies, more research will be needed before we can think seriously
about human applications.
Figure
2. Receptor Systems Involved in CBD’s Potential Therapeutic Applications.
CBD interacts, either directly or indirectly, with many different receptor
systems in the brain. It indirectly influences the major cannabinoid receptor
in the brain by decreasing THC’s ability to stimulate this receptor. It also
interacts with a variety of other receptors. A subset of these are shown here.
Each red shape represents a different brain receptor that might be found on a
neuron. Some of the potential therapeutic applications associated with CBD’s
interaction with each receptor system are listed below each receptor.
CBD: Psychiatric Utility From Complex Pharmacology?
Understanding CBD’s neurological effects
is a complicated business, because of the wide variety of receptors with which
it interacts. But that complexity may be the key to its promise as a
therapeutic agent. Motivational disorders like addiction and anxiety are
themselves highly complex; they arise from incompletely understood causes that
span multiple receptor systems and neural networks in the brain. CBD’s complex,
multi-target effects may therefore be crucial to its potential for aiding the
treatment of such disorders. Over the coming years, researchers will continue
to further understand this complexity and uncover the full scope of CBD’s therapeutic
potential.
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