Marijuana, THC, and the Science of Pain Relief

Several years ago I tried to do a backflip into the ocean and hurt my back. Immediately, my quality of life went from a 9/10 to a 6/10. Luckily, this was temporary, but many people suffer from chronic pain for months and even years. Over 20% of American adults suffer from chronic pain that lasts more than 3 months.^[1,2] This type of pain frequently fails to respond to standard treatments, and some options, such as opioids, have significant risks of serious side effects. As a result, several patients have turned to one of the oldest cultivated plants harvested by humans: cannabis.^[3]

Cannabis, also known as marijuana, has been harvested for at least four thousand years, which is longer than the alphabet has existed.^[3,4] It has been used for ceremony, recreation, and as a surgical anesthetic.^[3] The main psychoactive ingredient - the one that gives people the characteristic “high” of marijuana - is THC (Δ9-tetrohydrocannabinol).^[5] To understand how this drug may help manage pain, we first need to explore how neurons work in signaling pain.

Pain is a signal that is particularly effective at alerting us when something is wrong with the body. This signal originates in nociceptive neurons and travels to other neurons in the spinal cord and brain.^[6,7] However, when neurons are damaged, pain signals may be sent even without a harmful stimulus.^[6,7] This nerve damage-related pain, called neuropathic pain, can cause intense reactions to even mild stimuli. It may also make sensations that are normally painless feel painful.^[6,7] With chronic pain, neurons can develop maladaptive brain circuits that reinforce pain signals and can’t be easily reversed.^[8]

A cartoon showing one neuron (background) receiving pain signals.
Inset: a closeup of a single synapse, with neurotransmitters (purple) moving across the gap.

Zooming in a bit, let’s look at how neurons work. Neurons are cells that transmit information over long distances. In fact, the longest cells in our bodies are the sciatic neurons, which can be nearly three-feet-long and transmit information from our toes to the lower spinal cord! When we experience pain, peripheral neurons - located outside the brain and spinal cord - detect damage or harmful stimuli to the body and transmit this information to the central nervous system for processing. We perceive pain in the brain, so this signal has to travel up the body and spinal cord. The signal travels through individual cells using electricity. Neurons do not physically touch each other, so to transfer information between neurons, the signal has to cross a tiny gap called a synapse. 

In the synapse, we see where the THC in cannabis can have an effect. Synapses are tiny, (mostly) one-way gaps where one neuron sends a signal to another. THC reduces the synapse signaling by binding to two cannabinoid receptors.^[6] These cannabinoid receptors are named cannabinoid receptor 1 (CB1, found in the brain and spine) and cannabinoid receptor 2 (CB2, found in immune cells).^[3,5,6,9,10] Levels of CB2 receptors increase in response to neuropathic pain, with higher concentrations generally associated with greater pain intensity..^[11] When THC binds to CB1 and CB2 receptors, it may decrease the strength or frequency of the signal across synapses, thereby inhibiting pain signals from reaching the brain.^[9,10,11] The delayed time it takes for CB1 and CB2 receptors to form in pain-transmitting regions may help explain why marijuana is generally more effective at relieving chronic pain compared to acute, immediate pain.^[11]

This all sounds great, but marijuana use should be considered in a broader context. Firstly, marijuana remains illegal in many regions, and mere possession could land someone in jail. Secondly, the concentration of the main ingredient, THC, isn’t well controlled in street weed, leading to unpredictable effects. Average THC concentrations have increased from 4% to 12%, and some varieties may have THC levels as high as 30%!^[3] This can increase even further when using other forms of cannabis, such as hashish oil.^[11] With higher concentrations of THC, the side effect profile increases and may be undesirable for many patients. It can be important, therefore, to seek cannabis treatments that are vetted, controlled, and that come with the backing of randomized, controlled clinical trials. Research scientist Dr. Erich Schramm notes that for those with chronic pain,

"Patients can consider cannabis as a viable treatment option, especially in those patients trying to avoid opiate pain medications or traditional anti-inflammatory medications, like Motrin, Aleve, or ibuprofen."

For individuals living with chronic pain, participation in cannabis-based clinical research studies may offer new opportunities for pain relief and contribute to advancing treatment options. Interested patients are encouraged to explore ongoing clinical trials to determine eligibility and potential benefits.

Creative Director Benton Lowey-Ball, BS, BFA

References:

^[1] Rikard, S. M. (2023). Chronic pain among adults—United States, 2019–2021. MMWR. Morbidity and Mortality Weekly Report, 72. https://pmc.ncbi.nlm.nih.gov/articles/PMC10121254/

^[2] Knopp, K. L., Downing, A. M., Anthony, L., Chaterjee, S., Price, K., & Sparks, J. (2024). An innovative phase 2 chronic pain master protocol design to assess novel mechanisms in multiple pain types. Pain Reports, 9(6), e1203.https://pmc.ncbi.nlm.nih.gov/articles/PMC11487222/

^[3] Grant, K. S., Petroff, R., Isoherranen, N., Stella, N., & Burbacher, T. M. (2018). Cannabis use during pregnancy: pharmacokinetics and effects on child development. Pharmacology & therapeutics, 182, 133-151. https://www.sciencedirect.com/science/article/abs/pii/S0163725817302243

^[4] Rollston, C. (2020). The emergence of alphabetic scripts. A companion to ancient near eastern languages, 65-81. https://doi.org/10.1002/9781119193814.ch4

^[5] Henson, J. D., Vitetta, L., & Hall, S. (2022). Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions. Inflammopharmacology, 30(4), 1167-1178. https://link.springer.com/article/10.1007/S10787-022-01020-Z

^[6] Sokolaj, E., Assareh, N., Anderson, K., Aubrey, K. R., & Vaughan, C. W. (2024). Cannabis constituents for chronic neuropathic pain; reconciling the clinical and animal evidence. Journal of Neurochemistry, 168(11), 3685-3698. https://onlinelibrary.wiley.com/doi/full/10.1111/jnc.15964

^[7] Borges, J. P., Mekhail, K., Fairn, G. D., Antonescu, C. N., & Steinberg, B. E. (2021). Modulation of pathological pain by epidermal growth factor receptor. Frontiers in Pharmacology, 12, 642820. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.642820/full

^[8] Apkarian, A. V., Baliki, M. N., & Geha, P. Y. (2009). Towards a theory of chronic pain. Progress in neurobiology, 87(2), 81-97. https://www.sciencedirect.com/science/article/abs/pii/S0301008208001135

^[9] Bie, B., Wu, J., Foss, J. F., & Naguib, M. (2018). An overview of the cannabinoid type 2 receptor system and its therapeutic potential. Current Opinion in Anesthesiology, 31(4), 407-414. https://journals.lww.com/co-anesthesiology/abstract/2018/08000/an_overview_of_the_cannabinoid_type_2_receptor.5.aspx

^[10] Shahbazi, F., Grandi, V., Banerjee, A., & Trant, J. F. (2020). Cannabinoids and cannabinoid receptors: The story so far. IScience, 23(7). https://www.cell.com/iscience/fulltext/S2589-0042(20)30488-0

^[11] Vučković, S., Srebro, D., Vujović, K. S., Vučetić, Č., & Prostran, M. (2018). Cannabinoids and pain: new insights from old molecules. Frontiers in pharmacology, 9, 416167. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.01259/full?fd=5919341930653900|5317710456904024&lp=/CBD-cure-pelvic-pain