This article was originally published on the Spectrum Therapeutics Canada site.

When you go for a run on a summer day, your heart rate increases, you get hot and begin to sweat, and your breathing gets shallower and faster. When you stop running and sit in the shade, your heart slows to its resting rate, you cool off, and your breathing returns to normal. How is your body able to constantly adjust to changes like these?

We have a complex communication network between the nervous system, organs, and cells that makes sure our bodies function as well as possible. This network uses chemical signals to send messages from one cell to the next. These messages are received by specialized proteins on the cell surface called receptors.

Think of a receptor like a lock. The chemical message is the key that fits snugly into and unlocks the receptor. This changes the shape of the receptor, which then can transmit the message into the cell.

Enter the endocannabinoid system

Many receptors are part of a newly discovered part of this communication network called the endocannabinoid system (ECS), which exists in all vertebrates, including humans. The ECS plays an important role in maintaining the body’s normal way of doing things. It is involved in the development of our brain and nervous system, the way our immune system functions, appetite and digestion, cardiovascular function, bone development, pain, reproduction, memory, our sleep/wake cycles, and the regulation of stress and emotions.

One of the best-studied receptors of the ECS is cannabinoid receptor 1, or CB1. CB1 is found on the cell surface of neurons and helps modulate signalling throughout the nervous system. One of the chemical signals that unlocks the CB1 receptor is called anandamide. It has effects that are similar to some of those of THC, like euphoria.

Instead of travelling forward from one neuron to the next—the route that nerve impulses travel—anandamide is released from the post-synaptic neuron, sent backwards across the synapse, and binds to CB1 receptors on the previous neuron. This binding sends a signal into the previous neuron, telling it to stop releasing its chemical messenger (neurotransmitter), and thus dampening the message the previous neuron is sending.

But what does this mean for medical cannabis?

Here’s where it gets really interesting. Cannabis sativa also makes molecules that can interact with our ECS. Just like anandamide, plant-derived THC binds to the CB1 receptor, causing the same kind of changes in neurons that anandamide does (Di Marzo et al. 2011; Pertwee 2008). For example, pain signals are transmitted from nerve to nerve along pain-processing networks. THC can dampen this signal when it binds to the CB1 receptor—inhibiting neurotransmitter release from the presynaptic neuron—which can lead to pain relief (Bushlin et al. 2010; Parolaro et al. 2010). Cannabidiol does not bind to CB1. Instead, it exerts its effects by interacting with many other molecules in the body, including other receptors, such as the serotonin receptor (for more see Section 2.1 Pharmacodynamics in Health Canada 2018).

Scientists keep finding new receptors that are part of the ECS and determining how cannabinoids like THC and CBD interact with them. It will be from ongoing research that we will be able to expand our understanding of these receptors that are part of this complex communication network.

References

Bushlin I, Rozenfeld R, Devi LA. Cannabinoid-opioid interactions during neuropathic pain and analgesia. Curr Opin Pharmacol 2010 02;10(1471-4973; 1471-4892; 1):80-6.

Di Marzo V, Piscitelli F, Mechoulam R. Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes. Handb Exp Pharmacol 2011(0171-2004; 0171-2004; 203):75-104.

Health Canada. Information for Health Care Professionals. 2018. https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids-eng.pdf

Parolaro D, Rubino T, Vigano D, et al. Cellular mechanisms underlying the interaction between cannabinoid and opioid system. Curr Drug Targets 2010 04;11(1873-5592; 1389-4501; 4):393-405.

Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 2008 01;153(0007-1188; 0007-1188; 2):199-215.