What is pain? what causes it? how does it works and how do we treat it?

By John Carberry 

Pain is a process in our biology that includes a class of eicosanoids called opioid peptides. These are made de novo in our bodies; our bodies make them naturally and the rise from eicosanoid cascades.

We can start with a definition of three classes of pain treatments: two are very dangerous and not very efficacious. We can observe and conclude that Nonopioid analgesics (NSAIDs) and Opioid analgesics are very dangerous and ineffective. We can concluded CBD, as a precursor for making arachidonic acid which leads to making eicosanoids, can aid in the strong function of eicosanoids to mediate pain and heal.

Pain is registered by the brain and nervous system through nociception. It begins with a nociceptor, which is a sensory neuron. It is stimulated by damage or damaging stimuli and sends signals through the spinal cord to the brain. The brain then creates the sensation of pain centered on the specific site of the stimulation.

Where there is pain, there is also inflammation. The source of the pain is almost always a biological crisis the body is geared to cure and solve. So eicosanoids are involved in:

  • The signaling of pain,
  • The mitigation of pain and
  • The solution to the source of the pain.

Eicosanoid and endocannabinoid systems (ECS) are thus everywere engaged. These mechanisms are all engaged together and are related and interdependent, interacting. Pain is one of three things happening, we need to aid all three.


When there is a pain stimulus caused by a trauma event raising toxic antigens the ECB and eicosanoid systems engage at the same time. All three systems are stimulated to react together with inflammatory eicosanoid biosynthesis. CBD as a precursor to arachidonic acid, addresses all three systems in that arachidonic acid is a precursor to all three pathways.


This begins with the release of arachidonic acid (AA) from membrane phospholipids. CBD is a major sustaining agent in making AA available to the eicosanoid system. As pain is signaled, the system reacts with inflammatory signaling eicosanoids, and then later in the resolution phase, with anti-inflammatory signaling eicosanoids. The AA is eventually transformed thereby into cyclooxygenase (COX) and lipoxygenase (LO) pathways to prostaglandins, thromboxane and leukotrienes as typical types of eicosanoids. It is also involved in the making of opioid peptides which mediates pain.

These pathways are a major theme in non-opioid treatments for pain and inflammation. CBD in abundance, made de novo from the ECS system or taken as a supplement, thereby is intimately and powerfully involved in these events.  For example, nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase 2 (COX2) thus, decreasing the synthesis of prostaglandins. Some antiepileptic drugs and anesthetics thus inhibit the generation of pain nerve impulses.

The scholarship we are studying lead us to suggest that the optimal treatment for pain, would create also optimal inputs and conditions for the eicosanoid and ECS systems simultaneously.

Three classes of treatments for pain:

  • Nonopioid analgesics (nonopioids) include acetaminophen and other NSAIDs including aspirin and other salicylic acid derivatives. Acetaminophen, a nonopioid, appears to act mostly via a central mechanism. Most nonopioids have some anti-inflammatory, antipyretic, and analgesic effects, however, there is little anti-inflammatory effect by acetaminophen and it is a very dangerous liver toxin, injuring and killing many.
  • Opioid analgesics (opioids): mu opioid agonists (i.e., morphine-like agonists) and agonist-antagonist opioids; Opioids bind to opioid receptors in the central nervous system (CNS) to Inhibit the transmission of nociceptive input from the periphery to the spinal cord, activate descending inhibitory pathways that modulate transmission in the spinal cord, and alter limbic system activity and are powerfully and dangerously addictive, killing millions every year.
  • An adjuvant analgesic is a medication that has applications such as treating seizures, anxieity, depression and other afflictions but are also useful for other purposes, such as pain. These are also called co-analgesics. They suggest that these systems involving pain, inflammation and anti-inflammation are closely related. CBD approved by the FDA to treat severe seizures, appears to be one of the most broadly applied adjuvants of all time, surpassing aspirin.

Some notes to understand the three classes:

  • NSAIDs inhibit of the enzyme cyclooxygenase (COX) which blocks prostaglandin synthesis.
  • The discovery that COX has two isoforms, COX-1 and COX-2, is important to the advance of NSAIDs.
  • COX-1 is constitutively expressed in most normal tissues but plays an especially important role in the gastrointestinal (GI) tract, kidneys, and platelets. COX-1 primarily produces prostaglandins with beneficial effects (e.g., regulation of blood flow to the gastric mucosa and kidneys).
  • In contrast, COX-2 is normally not present but may be induced in response to inflammatory stimuli; COX-2 primarily produces prostaglandins that activates and sensitizes nociceptors.

Thus, opioids modify sensory and affective aspects of pain. However, eicosanoids seems to address all three systems in a balanced and healthful way and CBD aids these functions by being a powerful precursor for arachidonic acid. And it may be much safer than the other two.

FDA on danger of Opioids:

It should be noted that the term “opioids” has replaced “narcotics,” and “co-analgesics” is an alternate term for “adjuvant analgesics. Most everyone today is aware of the danger of narcotics. Just last year the FDA drafted this guidance for medical providers with respect to opioids: FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain (May 2017)

Opioid analgesics

HCPs should be knowledgeable about the risks associated with opioid analgesics as they pertain to their patients and from a public health perspective.

  1. Epidemic of prescription opioid drug abuse – HCPs should be knowledgeable about the extent of the problem. HCPs should understand that most of the opioids available for misuse and abuse in the community originate from prescriptions for individual patients.
  1. Paradigm shift in opioid prescribing – HCPs should be knowledgeable about existing information about safe opioid practices, current federal and state regulations, and guidelines on opioid prescribing and the use of naloxone.

Some references from the WHO on Safety:

We would also here quote the WHO on the safety of CBD: (WHO Expert Committee on Drug Dependence Thirty-ninth Meeting Geneva, 6-10 November 2017)

Adverse Reactions in Humans: As noted above, CBD does not produce the effects that are typically seen with cannabinoids such as THC. It also failed to produce significant effects in a human study of abuse potential discussed below. [39] Across a number of controlled and open label trials CBD of the potential therapeutic effects of CBD it is generally well tolerated, with a good safety profile.

Human Studies: While the number of studies is limited, the evidence from well controlled human experimental research indicates that CBD is not associated with abuse potential.

Understanding Pain, Inflammatory reactions, Anti-inflammatory reactions in the context of the pain, ECS and eicosanoid systems and regulations:

If CBD is safe, non-addictive, addresses a broad cross section of our biological operations, if it is safer and more efficacious than opioid and non-opioid treatments, it should be preferred.  

For instance, Pisanti et. al.  (Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacology 2017. 175: p. 133-150):

We are reminded of Daniel Rossignol’s article Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism (DanielA.Rossignol1* and RichardE.Frye2 REVIEW ARTICLE 22April2014)

We quote:

Several case-control studies have reported Lower concentrations of reduced glutathione(GSH), higher levels of oxidized glutathione(GSSG)and a decrease in the GSH/GSSG redox ratio(Jamesetal.,2004,2006,2009b), along with a lower mitochondrial GSH reserve(Jamesetal.,2009a) in individuals with ASD compared to controls. In addition, in some studies, lower GSH levels(Adamsetal.,2009) and markers of increased oxidative stress (Ghezzoetal.,2013) have been correlated with ASD severity.

The reason this is relevant is that CBD, like astaxanthin and THC, is one of the few large molecules of value that crosses the blood brain barrier. So, it is likely that CBD and astaxanthin, especially in combination with a rich source of DHA, would be a great treatment to prevent to limit or eliminate the oxidative stress described here. Our Conclusions

  • A healthy eicosanoid system an effective treatment for pain (emboldened by my for emphasis): (T.R. Deer et al. (eds.), Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Integrative Approaches, 181 DOI 10.1007/978-1-4614-1560-2_18, © American Academy of Pain Medicine 2013) Basic science and clinical trials support the theoretical and practical basis of cannabinoid agents as analgesics for chronic pain. Their unique pharmacological profiles with multimodality effects and generally favorable efficacy and safety profiles render cannabinoid-based medicines promising agents for adjunctive treatment, particularly for neuropathic pain. It is our expectation that the coming years will mark the advent of numerous approved cannabinoids with varying mechanisms of action and delivery techniques that should offer the clinician useful new tools for treating pain. A healthy eicosanoid system is aided by the ROS mitigation rising from astaxanthin.
  • Since CBD does not have a strong affinity for either the CB1 or CB2 receptors in the nervous system and brain, nor with the CB2 receptors in the immune and endocrinal systems, and since it does interact powerfully with the eicosanoid system to liberate AA from the phospholipids in the plasma membrane, it is clear that CBD/eicosanoid interactions play a powerful role.
  • Per Pisanti’s profile above CBD has many beneficial functions and effects; 
  • Per the WHO report, there was no difference in evaluating safety and addiction between CBD and placebo and it was found to be probably safe; 
  • Healthy Eicosanoid systems attenuates pain while aiding the ECS and Eicosanoid systems in resolving the cause of the pain at the same time. Of the three, I conclude the Opioids and NSAIDs are dangerous and I conclude a healthy eicosanoid function is the safest and most efficacious by far. 
  • The eicosanoid system’s many cascades require freedom from ROS, but also require a lot of energy, which must come from the body’s powerhouse, the mitochondria. Astaxanthin protects the mitochondria from oxidative energy, so a strong expression of bio available astaxanthin in the cell membranes and mitochondria membranes enables the body’s powerhouse to make the energy the body requires, that all the eicosanoid storms require.