How does CBD work its magic? The body uses cannabinoids not only to upregulate the endocannabinoid system (ECS), but also to stimulate and regulate pathways outside of the ECS. CBD has 65 known targets for activity in the brain and body outside of cannabinoid receptors. Let’s explore these below!
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Glycine Receptors
These are extremely abundant throughout the spinal cord as they are responsible for receiving messages from the body and sending them to the brain. These receptors are mechanisms by which the body decreases inflammation in neuropathic pain. CBD is able to upregulate these receptors.
GABA
Maybe the key to reducing depression? CBD works to increase levels of GABA in the body. GABA’s job is to turn down excitatory pathways—this is one route by which the body is able to produce anti-stress and anticonvulsant effects.
GPRSS
These receptors are associated with cancer, pain, obesity, diabetes, bone health, and GI motility. They have been found to promote seizure cycles, cancer cell metastasis, upregulate obese and Type 2 DM, and upregulate osteoporosis. CBD is an antagonist to this receptor, therefore blocking the receptors’ activation. It does this while decreasing glutamate (which decreases neuronal excitability) and increasing GABA (which increases neuronal calming).
5HT1A & 2A
These receptors are associated with anxiety, appetite, sleep, pain, addiction, nausea, and vomiting. CBD’s ability to bind directly to these receptors increases the efficacy of these receptors and helps the body’s own serotonin work more effectively. Increased affinity in these receptors are known to result in effects that are protective, analgesic, uplifting, stress reducing, and nausea reducing.
PPARy
Cannabinoids can activate PPARy receptors. These are nuclear receptors found on the nucleus’s cell wall. They are involved in lipid storage, energy/glucose metabolism, cell differentiation, and regulating inflammation; they can be utilized clinically to treat cholesterol, triglycerides, and insulin resistance. These receptors are also studied for their anti-cancer, neuroprotective, and anti-gut inflammation effects. Additionally, these receptors can decrease insulin resistance and degrade amyloid plaque in the brains of those with Alzheimer’s.
Adenosine Receptors
These play a part in cardiac rhythm/circulation, renal blood flow, immune function, sleep regulation, inflammatory disease, and neurodegenerative disorders. By binding to Adenosine A1 receptors, cannabinoids can promote anti-arrhythmic effects. By binding to Adenosine A2 receptors, cannabinoids can support anti-inflammatory effects. In addition, extra cannabinoids in the system can help the adenosine receptors create more extensive neuroprotective effects.
Opioid Receptors
Opioid pathways work by enhancing endorphins, both of which are stimulated by cannabinoids.
GPR18
This is thought to be a third cannabinoid receptor, hopefully the future will bring more clarification to this hypothesis. It is especially important to immune and microglia function. Microglia acts as the primary defense of the immune system for the brian and spinal cord.
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Enzymes
CBD interacts with 32 enzymes, specifically the cytochrome P450 enzyme which
controls the metabolism (and is why we must be careful of certain drug interactions), the mitochondrial electron transport chain enzymes which modulate brain energy metabolism, the AANAT enzyme which creates melatonin biosynthesis, the FAAH enzyme which degrades endocannabinoids, the COX/LOX enzymes which play a part in inflammation, and the IDO enzymes which are involved in cytokine-induced sickness behaviors.
Ion channels
CBD targets ten different ion channels. Ion channels sit on cell membranes and facilitate movement of ions through the membrane; there are calcium, potassium, and sodium ion channels that are responsible for regulating the heartbeat, neuron function, muscle contractions, and more. This process is implicated in thermoregulation, pain, anti-inflammation, anti-cancer, and anticonvulsant effects. In the case of Charlotte Figi, what she had was an ion channel dysfunction.
Transporters
Transporter proteins move chemical compounds through the brain and the body. CBD is able to bind to transport proteins and block the reuptake of endocannabinoids, therefore stopping the breakdown of the cannabinoids produced by the body. This allows more cannabinoids to circulate throughout the body, enhancing signaling of the cannabinoid receptors, creating a natural state of peace and homeostasis.
An Article By Evie Louise
Evie Louise is a recent psychology graduate from New York University. She is a certified in International Cannabinoid Clinical Therapy. Evie sees all forms of the cannabis sativa plant as the future of psychiatry, and hopes to use it in her therapy practice as a full spectrum approach to mental health and wellness.
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