Science amp; Tech Cannabis research on the evolving science behind its effects and the latest technology news. Science amp; Tech CBD and the Brain: What Does It Do and What is it Good For? Nick Jikomes 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 dont always lead to the clinical application that we hope forthe 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. RELATED STORY CBD Holds Promise as Child Epilepsy Treatment Studies Find Whats the biological basis for this wide range of potential medical uses? A key part of the answer lies in CBDs promiscuous pharmacologyits 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 neurons 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 cant. 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 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 youre 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 dont interact with all neurons just the ones that have the appropriate receptors. RELATED STORY Cannabinoids 101: What Makes Cannabis Medicine? 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-psychoactive (see Bruce Barcotts article tomorrow). In addition to its indirect influence on the CB1 and CB2 receptors CBD can increase levels of the bodys 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-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. RELATED STORY Can Cannabis Help Treat Painkiller and Heroin Addiction? This raises the intriguing possibility that CBDs 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 Rahns article later this week). However we cant say for sure at this point; more research on CBDs interactions with the opioid and dopamine receptor systems is still needed. CBDs 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. CBDs 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 Kossens article later this week). RELATED STORY The Effects of CBD on Fear Anxiety and a Healthy Stress Response CBD and the serotonin system: exciting possibilities CBDs 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. Its 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. CBD: psychiatric utility from complex pharmacology? Understanding CBDs 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. CBDs 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 CBDs therapeutic potential. References Blessing EM Steenkamp MM Manzanares J Marmar CR. Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics. 2015;12(4):825-36. [PDF] Mechoulam R Parker LA. The Endocannabinoid System and the Brain. Annu Rev Psychology. 2013;64:21-47. [PDF] Morgan CJ Schafer G Freeman TP Curran HV. Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study: naturalistic study. Br J Psychiatry. 2010;197(4):285-90. [PDF] Parsons LH Hurd YL. Endocannabinoid signalling in reward and addiction. Nat Rev Neurosci. 2015;16(10):579-94. PDF Zlebnik NE Cheer JF. Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?. Annu Rev Neurosci. 2016;39:1-17. PDF Nick Jikomes cbdCBD Weekhealthresearch Nick Jikomes Nick is Leafly's senior science advisor. He completed his PhD in neuroscience at Harvard University in 2016. Related Articles What are High CBD Cannabis Strains and How Do They Differ from High THC Strains? Which Cannabis Strains are High in CBD? High CBD Products for Medical Marijuana Patients Can CBD Undo the Anxious Side Effects of THC? Close Sign Up for More Leafly News Thank you for subscribing! Email Sign Up By submitting this form you will be subscribed to news and promotional emails from Leafly and you agree to Leafly's Terms of Service and Privacy Policy. You can unsubscribe from Leafly email messages anytime. More CBD Science Health How Does Cannabis Consumption Affect the Brain? Health How Effective is CBD On Its Own? Health Can Cannabidiol (CBD) Help Support Weight Loss and Metabolism? Science amp; Tech Science Revisited: Will Using CBD Hemp Oil Lead to a Positive Drug Test for THC? The post CBD and the Brain: What Does It Do and What is it Good For? appeared first on Leafly. by Nick Jikomes at Leafly