Medical Cannabis for Pain: An Overview

Summary

Every health problem involves a type of pain, whether physical, mental, emotional, or spiritual. Medical cannabis is often used for pain relief, particularly chronic pain, and it is the most common reason people turn to cannabis.

The plethora of anti-inflammatory compounds in cannabis, its safety profile, ability to target and bind to multiple receptor systems, and efficacy as a replacement for opioid-based medications are some of the main reasons it may be so helpful for managing so many different types of pain. This is also why Leafwell dubs cannabis a “pharmacy in a plant.”

We have an extensive entry on cannabis for chronic pain management, which we have written for patients interested in learning why medical cannabis and gives more details on specific phytocannabinoids, terpenes and flavonoids, and THC:CBD ratios that may be useful.

Introduction: What is Pain?

Pain is often put into one of two broad categories: acute pain, which is sudden pain that is usually sharp in quality and is a typical response to pain arising as a response to injury (e.g., a sprained ankle, broken bone, or surgical pain); or chronic pain, which is pain that carries on for longer than 12 weeks (3 months) despite medical treatment or medications. Chronic pain can result from a long-term, chronic health problem or injury.

Four types of pain feed into one another and should not necessarily be seen as separate:

1. Physical pain
2. Psychological pain
3. Social pain
4. Spiritual pain

Dame Cicely Saunders, considered the mother of the hospice movement, thought pain to be multidimensional, coining the term “total pain” to describe the combined aspects of the above types of pain.

Musculoskeletal pain is the easiest to identify and measure due to the classic symptoms seen in specific body parts, notably the bones, joints, ligaments, muscles, and tendons. The three main types of physical pain include:

1. Nociceptive pain
2. Neuropathic Pain
3. Nociplastic pain

Nociceptive Pain

Nociceptive pain involves damage to body tissue often caused by an external force or overuse, such as bruises, sprains, burns, fractures, and joint damage. It is a pain that feels sharp, aching, or throbbing. Nociceptive pain is often divided into two main subcategories:

1. Visceral pain. Occurs when internal organs become inflamed or injured, often aching pain. The most common forms of visceral pain are functional gastrointestinal disorders (FGID) like irritable bowel syndrome (IBS) and severe pelvic pain, usually as a result of dysmenorrhea (severe cramps and menstrual pain during a woman’s period).
   
   Visceral pain can be difficult to locate due to its diffuse nature. For example, visceral pain can cover whole areas of the body or occur in one part when the problem is in another part of the body. Visceral pain is often described as sickening, deep, squeezing, or dull, accompanied by nausea, vomiting, and anxiety. Examples of visceral pain include stomach aches or kidney stones.
2. Somatic pain. Originates in the arms, legs, face, muscles, tendons, and other superficial body areas. Somatic pain occurs when pain receptors in the skin, muscles, skeleton, joints, and connective tissues are activated, typically by stimuli such as force, temperature, vibration, or swelling. Examples of somatic pain include bone fractures, osteoporosis, arthritic pain, cuts, scrapes, and burns.

Neuropathic pain

Often called “nerve pain,” neuropathic pain is caused by nerve damage or injury, and this can lead to misfiring and incorrect brain and spinal cord signals to the skin, muscles, and other body parts. Neuropathic pain is often described as a shooting or burning.

Causes of neuropathic pain include spinal cord diseases or injuries, medication side effects, diabetes, burns, neurological conditions such as multiple sclerosis (MS) or epilepsy, cancer and cancer treatment, viral infections, trigeminal neuralgia (TN), and alcoholism.

Nociplastic pain

Nociplastic pain is not well understood but is thought to be caused by dysfunction (possibly hyperexcitability) in the central nervous system (CNS) and/or immune system.

Nociplastic pain is a complex, long-term type of pain defined as “pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain.” Nociplastic pain is usually used to describe the pain associated with fibromyalgia, chronic fatigue syndrome (CFS), temporomandibular disorder, and some types of headaches/migraines.

How is Pain Treated?

How pain is treated depends very much on the type of pain one is experiencing. Common medications for different kinds of pain include:

• Visceral pain. Over-the-counter (OTC) analgesics like acetaminophen (Tylenol, paracetamol); non-steroidal anti-inflammatories (NSAIDs) such as Aleve (naproxen) and aspirin (acetylsalicylic acid); opioids (usually for acute and surgical pain, but also some types of chronic pain).
• Somatic pain. Many of the same drugs as visceral pain. Steroids like prednisolone may also be prescribed to manage pain associated with osteoporosis and arthritis.
• Neuropathic pain: anti-convulsant medications are often prescribed, like gabapentinoids (e.g., pregabalin and gabapentin); benzodiazepines like clonazepam; and carboxamides like carbamazepine.
• Emotional aspects of pain: antidepressants can help manage anxiety and depression often associated with pain. Antidepressants are often prescribed for all types of pain, particularly neuropathic pain.
• Nociplastic pain: traditional pain medications like NSAIDs, anticonvulsants, antidepressants, and opioids often have limited efficacy for nociplastic pain. The most common medications for this type of pain include analgesics like acetaminophen, NSAIDs like ibuprofen, and antidepressants like venlafaxine, duloxetine, and amitriptyline.

Non-drug pain intervention methods include:

• Exercise
• Following an anti-inflammatory diet
• Acupuncture
• Electrical stimulation
• Massage
• Hypnosis
• Mental health therapy
• Physiotherapy

Many also turn to herbal medications like turmeric, black pepper, lavender, cloves, capsaicin, ginger, and ashwagandha to help manage chronic pain.

Why Might Cannabis Treat or Manage Chronic Pain? The Role of the Endocannabinoid System (ECS) in Pain Detection

We are still learning about the endocannabinoid system (ECS) and its various roles in the human body. The ECS is intimately connected to homeostasis, which is “a self-regulating process by which biological systems maintain stability while adjusting to changing external conditions.”

The ECS plays a vital role in inflammation and immune response, pain detection, the sleep-wake cycle, mood, memory formation, appetite regulation, reproduction, and fertility.

When the ECS is dysfunctional, this can lead to an abundance of stress, leading to inflammation, which is a part of almost every disease or injury.

Phytocannabinoids from cannabis, including tetrahydrocannabinol (THC), cannabidiol (CBD), and beta-caryophyllene, can help reduce inflammation by returning balance to various physiological processes and reducing the release of stress hormones like cortisol.

Inflammation is not always harmful, but when out of control can lead to numerous health problems.

This dysfunction (or “endocannabinoid dysregulation”) can be found in pain detection as well, where the endocannabinoid system works to regulate pain signals:

 EC [endocannabinoids] are thought to act as a brake on neuronal hyperactivity, being produced in response to high levels of stimulation and feeding back negatively on the circuit through interaction with pre-synaptic cannabinoid receptors. In pain pathways, these actions produce analgesia by inhibiting the transmission of pain signals.

So, if the body is not producing the appropriate amount of cannabinoids or if there is a problem with how cannabinoid receptors (CB1 and CB2) are functioning, then the transmission of pain signals is not adequately inhibited. The amount of analgesia the body can naturally produce is reduced.

Cannabinoid receptor distribution and concentration throughout the body (endocannabinoid tone) also make a difference in terms of the type and location of the pain.

CB1 receptors are found predominantly on nerve cells, with CB2 receptors on immune system cells. CB1 receptor agonists like anandamide (the “bliss molecule”) and partial CB1 agonists like THC can bind to CB1 receptors and provide relief and relaxation that can help manage pain, especially related to spasms, stress, and nociceptive pain.

CB1 receptor antagonists can potentially help manage metabolic disorders like diabetes and obesity. CB2 receptor agonists like beta-caryophyllene (more accurately a selective CB2 receptor agonist) help manage pain associated with inflammation and neurological disorders, e.g., arthritis and epilepsy.

Useful Cannabis Compounds (Cannabinoids, Terpenes, Flavonoids)

Cannabis contains many compounds that can help reduce pain, transmit pain signals, and inflammation in various ways. The different compounds synergize and enhance each other’s anti-inflammatory effects via the entourage effect.

Phytocannabinoids

• THC and CBD act on key opioid receptors (mu-, kappa– and delta-opioid receptors), which can reduce inflammatory pain and modulate how pain signals are communicated to the brain.
• CBD does not bind to cannabinoid receptors but does enhance anandamide signaling, leading to an increase of anandamide in the body and helping improve mood. Reducing anxiety is a huge part of pain control.
• CBD also modulates serotonin transmission, which can also help improve mood and reduce pain.
• CBD is also thought to desensitize TRPV1 receptors, which are involved in pain detection and are sometimes thought of as a third type of cannabinoid receptor.
• CBD also inhibits the COX-2 enzyme, alleviating inflammatory pain similarly to ibuprofen but with fewer side effects.
• The acidic, non-decarboxylated forms of THC and CBD, tetrahydrocannabinolic acid (THCA), and cannabidiolic acid (CBDA) are also thought to have anti-inflammatory properties.
• Minor cannabinoids like cannabigerol (CBG) and cannabichromene (CBC) also have anti-inflammatory properties that can help reduce pain.
• The phytocannabinoid tetrahydrocannabivarin (THCV) is a CB1 receptor antagonist in low doses and a CB1 receptor agonist in higher doses, meaning it can potentially help both reduce and enhance the psychoactivity of THC.
  
  THCV can reduce hunger in low doses and possibly induce hunger in higher doses. THCV may be beneficial for managing inflammation associated with metabolic disorders like diabetes.

Terpenes

• Atypical cannabinoids/terpenes like beta-caryophyllene have analgesic and anti-inflammatory properties that can help manage conditions like arthritis.
• Terpenes like myrcene, linalool, and pinene also have stress-busting and anti-inflammatory properties that help relieve pain.

Flavonoids

• The flavonoids in cannabis (e.g., cannflavins and quercetin), which contribute to its flavor and color, have significant anti-inflammatory effects. Cannflavins A and B “were found to have anti-inflammatory benefits 30 times more effective than Aspirin.”

A Pharmacy in a Plant: The Multi-Receptor Target of Cannabis

Cannabis contains many chemical compounds that help manage many kinds of pain. Indeed, it is arguable that cannabis is perhaps the only medication to alleviate total pain (physical, emotional, social, and spiritual).

The ability of cannabis to target and influence the behavior of cannabinoid, serotonin, dopamine, and opioid receptors, among others, is one of the reasons why medical cannabis can help reduce reliance on so many other medications that are prescribed for pain, including:

• Opioids
• Sedatives
• Antidepressants
• Non-steroidal anti-inflammatory medications (NSAIDs) like ibuprofen and aspirin
• Anti-convulsants

Some types of pain, such as neuropathic pain, are not well controlled by current prescription medications. Cannabinoids like CBD present hope that there are now some available, even if improvements in production and dosing information are needed (as well as more placebo-controlled clinical trials).

Data Overview

This data overview includes studies on chronic pain, cancer pain, central pain syndrome, generalized pain, menstrual pain, and associated conditions.

• Total Studies = 229
• Positive Studies = 200
• Inconclusive Studies = 26
• Negative Studies = 3
• 151 Meta-Analyses (124 positive, 24 inconclusive, 3 negative); 33 Animal Studies (all positive); 22 Double-Blind Human Trials (20 positive, 2 inconclusive); 14 Human Trials (all positive); 9 Lab Studies (all positive)
• 3 studies include CBD (all positive); 1 study includes THC (positive); 1 study includes CBC (positive)
• No. of Leafwell Patients (2021) = 22,000 for chronic pain specifically
• Possible Overall Efficacy: High

Pros and Cons of Medical Cannabis for Chronic Pain

Pros

• Cannabis contains a multitude of analgesic and anti-inflammatory compounds that can help reduce pain and inflammation.
• Cannabis can help reduce or even replace the intake of many medications, including addictive ones like opioids and sedatives.
• Evidence suggests that increased levels of anandamide in the body via suppressed fatty acid amide hydrolase (FAAH) inhibition reduce pain.
• Medical cannabis can be used to manage various types of pain, including chemotherapy treatment, cancer pain, and pain associated with multiple sclerosis (MS).

Cons

• Cannabis may not help manage extreme levels of pain, for example, acute pain associated with surgery.
• One study suggests that THC may increase some people’s pain sensitivity (while other studies indicate the opposite).
• One four-year study shows that cannabis is not necessarily effective for chronic pain.
• Some types of chronic pain may be cannabinoid-responsive, others less so or not at all. We still need to find out what types of chronic pain medical cannabis can help manage and who it might benefit most.

Overall

A solid body of scientific evidence supports medical cannabis and its constituents (in particular, cannabinoids, terpenes, and flavonoids) as a drug that can help manage different and varying types of pain. However, the true efficacy of cannabis for various kinds of pain still needs to be determined.