We have all heard the “This is your brain on Drugs” routine. But let’s take an actual evidence of what happens to your brain. Cannabidiol (CBD) is one of many cannabinoid molecules produced by Cannabis, second only to THC in abundance. These phytocannabinoids (phyto means plant in Greek) 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 include ongoing clinical trials that evaluate its efficacy in the treatment of human disorders; animal studies that investigate its behavioral and physiological effects, and lab work that measures 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. Meanwhile, animal studies and lab experiments allow researchers to explore their biological actions in greater detail. However, since we don’t conduct studies in humans, the results don’t always lead to the clinical application that we hope for. In fact, 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 that is where the initial breakthroughs in research.

 

 

What is CBD’s potential?

CBD is famous for childhood epilepsy treatment. 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 lab experiments, that CBD may have neuroprotective, anti-inflammatory and pain-relieving properties. It also may have 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 is its ability to influence a wide range of receptor systems in the brain and body, including cannabinoid receptors and a host of others.

 

 

Reach your Receptors.

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 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.

 

We have barely scratched the surface of the full potential of this compound CBD.

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Brain receptors are sensitive to neurotransmitters produced naturally within the brain, like dopamine or serotonin. They are 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 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’s influences on 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 CBD is non-psychoactive (see Bruce Barcott’s article tomorrow). 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.

Intriguing part of CBD

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-grade 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 the opioid or dopamine receptors may underlie its ability to dampen drug cravings and withdrawal symptoms, effects directly relevant to the treatment of addiction (see Bailey Rahn’s article later this week). However, we are not sure if we need more research on CBD’s interactions with the opioid and dopamine receptor systems.

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 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 (see Jeremy Kossen’s article later this week).

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