As I sit down to write about pain, I am reminded of how debilitating ongoing chronic pain can be. After all, I just spent the better part of the afternoon with awful back pain. I tripped on my way up the stairs and instinctively chose to rescue the delicious coffee I was carrying instead of using my otherwise catlike reflexes to cushion the fall. While I successfully managed not to spill any of the delightful black gold, I am paying for it with pain, sent to my brain by some muscles I didn't realize I had, that are now enthusiastically reminding me of their existence every time I move. The good news is, I could alleviate some of that pain with a puff of cannabis. The bad news is, I don't have any. However, what I do have is a primer on pain, the endocannabinoid system and medical cannabis which I am happy to share with you in the paragraphs below.
Pain is Good
At its core, the ability to experience pain is good, at least from a survival perspective. Pain is an evolutionary adaptation that warns us of ongoing or impending damage to our bodies. It is a way for our tissue cells to communicate to our brain and say things like: "Hey, if you don't take your hand off that flame, it will denature our proteins- adjust your behavior, doofus, or else we'll melt." Pain is complex, personal, unpleasant, and can range in intensity from slight, to severe, and even excruciating. However, it is not supposed to last forever.
There are 3 main overarching categories of pain mechanisms:
Nociceptive pain is what you experience when your peripheral nervous system warns you of impending or ongoing damage. For example, when you cut yourself, have an inflamed infection, or you pulled a muscle. The damaged tissue will send a message via a chain of afferent neurons (brain input neurons) through the spinal cord and into your brain. The pain will subside as the damage heals, and your brain will hopefully remember not to repeat the foolish behavior that got you into trouble in the first place.
The second mechanism is Neuropathic pain. It occurs when the neuronal pipeline itself is damaged and is now erroneously relaying a "pain message" to the brain that doesn't exist. This can also be caused by injury, but is mostly due to some diseased malfunction of the peripheral nervous system. For example, diabetics might suffer from diabetic neuropathy. A condition where you experience phantom foot pain because the disease attacks the peripheral nerves, resulting in an aberrant signal interpreted by the brain as pain.
Lastly, there is Centralized pain. Caused by the amplification of peripheral signals resulting from central nervous system dysfunction. Your brain is again receiving incorrect data. An apt metaphor would be a musical instrument that is nice and quiet until you plug it into an amplifier, becoming impossible to ignore.
Pain can be acute, in other words, immediate, sudden, and transient, or chronic and long-lasting. Chronic pain is defined as pain that persists after all possible healing has occurred and lasts more than 3 months despite treatment.
The Endocannabinoid system (ECS)
The endocannabinoid system regulates pain sensation through modular actions at all stages of the pain processing pathway. Its two primary receptors, CB1 and CB2, can be found throughout the peripheral, central nervous, and immune systems. CB1 is chiefly found on neurons, while CB2, principally but not exclusively, resides on immune cells. In a nutshell, their mode of action is to return activated cells back to a balanced state of homeostasis once their activation is no longer needed. So for pain transduction, everything starts with a noxious stimulus. This can be mechanical stress, heat damage, or even an infection. In the case of infection, the tissue-resident immune cells would sound the alarm and secrete various pain signals into the stimulus' general environment (histamine, serotonin, bradykinin, prostaglandin, IL-6, TNF-alpha, etc.). Cells of the peripheral nervous system can pass the pain signal along a chain of neurons from one cell to another until they reach the brain. Neurons are like information superhighways of the body that can transmit information over long distances and with low latency, from the periphery of your body to the brain.
In a nutshell, their mode of action is to return activated cells back to a balanced state of homeostasis once their activation is no longer needed.
Furthermore, they are location-specific, so the brain knows exactly where the pain signal is coming from. Neurons hand the information off at junctions between them called "synapses." This is where the endocannabinoid system is involved in modulating the signal. When a pain signal arrives at the junction, neurotransmitters are released by the input neurons into the synaptic gap between the cells. The transmitters diffuse towards the receiving cell, where they bind to specific receptors that cause the receiving cell to get "excited" and pass the signal along its own branches. Once the signal has been passed along, the receiving cell starts releasing endocannabinoids back (retrograde) into the synaptic gap. There they bind to cannabinoid receptors (CB1/CB2) of the input neuron, returning it to its standby state. After a while, the cannabinoids are metabolized by enzymes (FAAH / MAGL). The cannabinoid receptors are cleared, and the input neuron is ready to send the next pain signal.
Cannabis as Therapy
The synaptic interface is where phytocannabinoids,such as cannabis-derived cannabinoids, THC and CBD, can act on pain transmission. Phytocannabinoids will activate the cannabinoid receptors just like the body's own endocannabinoids would. However, THC has a high affinity and isn't metabolized as fast. So the input neuron is forced to remain in its "standby" mode for longer and cannot release a second wave of activating neurotransmitters. Similarly, pain signals secreted by immune system cells are also reduced. Furthermore, studies have shown that THC's psychedelic properties also affect the subjective perception of pain, improve mood and help patients sleep, thus lowering the secondary impact of chronic pain.
With the absence of long-term therapies lacking significant side effects, managing chronic pain is challenging. Alleviation of chronic pain can induce euphoria, so there is also a high addiction potential associated with anti-pain medications. Different first-line and second-line approaches against pain exist today, such as "anti-inflammatory drugs (NSAIDs), opioids, local anesthetics, antidepressants, and anticonvulsants. Herbal cannabis, cannabis-derived, and synthetic cannabinoid treatments now constitute a third-line option. In addition to pain management, cannabis could also help mitigate some addiction potential. THC has been shown to prime the brain for other drugs, such as opioids, enhancing their effects. Thus it is possible to lower the opioid dose when combined with THC and still achieve similar analgesic effects.
For medical purposes, the correct dosage is the minimum dose required to achieve the therapeutic effect.
However, it is essential to understand that the medical science supporting cannabis-based therapies for pain is young and insufficient. Cannabis cannot be viewed as a silver bullet against pain, as we don't have a complete clinical picture of it yet. However, there is enough scientific evidence to suggest that cannabis could be a valuable addition to the anti-pain toolbox. It is worth investing in more controlled clinical studies, as pain is impactful both socially and economically. A vast majority of hospital visits occur as a direct result of pain. Estimates attribute between $500-$600 billion of yearly medical expenses to chronic pain management in the US alone.
As of today, there is insufficient scientific evidence to clearly decide whether herbal cannabis, cannabis-derived, or synthetic cannabinoids differ in their efficacy, tolerability, and safety. As far as we know, cannabis oils have similar safety profiles as herbal cannabis.
Doctors will typically only prescribe herbal cannabis, cannabis-derived, or synthetic cannabinoids when conventional first-line or second-line treatments have either failed or proven to be too disruptive. Also, there are situations where cannabis consumption itself is risky and should be avoided. For example, pregnant or lactating women, children, adolescents, people with a history of substance abuse, psychosis, or severe cardiac disorders, should avoid cannabis for pain management. Cannabis products can have both pharmacokinetic and pharmacodynamic interactions with other drugs, so never consume cannabis in combination with other drugs without checking if it is safe. For example, avoid taking cannabis when taking high doses of benzodiazepines or opioids, as cannabis will amplify their effects. In that vein, it is also important to stop consuming it if you are about to go into surgery, or at the very least, inform your anesthesiologist, since those drug interactions extend to common anesthetics as well.
A mix of THC/CBD seems to be the most effective, but you should not go beyond 12.5% THC content.
Finding your individual dosage will be a process, with age, body weight, and sex, playing a role in deciding what that dosage is. For medical purposes, the correct dosage is the minimum dose required to achieve the therapeutic effect. Dosing higher than that risks exacerbating adverse effects and running into tolerance and addiction problems. Using registered cannabis extracts with defined and standardized THC and THC/CBD content will make calibrating that dose easier. A mix of THC/CBD seems to be the most effective, but you should not go beyond 12.5% THC content. For herbal cannabis, consuming 25mg-50mg of no more than 12.5% THC three times per day, seems like a good starting point, but definitely consult with your doctor on this. As for the mode of delivery, it is typically best to avoid smoking cannabis and instead use sublinguals, cannabis oils, or inhale it via temperature-controlled, electrically-driven, vaporizers. This should help minimize the risk of unnecessarily damaging your lungs.
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