Chronic pain & cannabinoids: what your drugstore is hiding you

Chronic pain


 Neuropathic and inflammatory pain

Nociception (pain perception) is a critical mechanism of the body self-defence, inducing to discontinue a stimuli potentially deteriorating.

When pain is experienced chronically, often as a consequence of a neural or metabolic dysfunction, as in the case of neuropathic pain (NP), it is fundamental to find agents able to target the pathways producing allodynia (sensation of pain evoked by a stimulus which would not, normally, produce it) and ultimately to eradicate them. [1]

It has been estimated that 7-8% of the entire population of Western Countries develops neuropathic pain, which is often caused by other pathologies (cancer, diabetes, MS, HIV or stroke, just to mention a few).[2]

Despite the aetiology of the disease is multifarious, it causes the nervous system to be hypersensitised due to prolonged impulses.

Neuropathic pain alone is a chronic debilitating disease that affects up to 4 million people just in Europe; given the poor outcome of the medicines currently in use for the management of symptoms, (gabapentin, opioids and tricyclic antidepressant mainly) many studies are focused on this field of study. [3]


Why using cannabinoids for chronic pain?

Phytocannabinoids have been extensively used throughout history for various therapeutic purposes, particularly analgesic. However, the cannabinoid circuitry is relatively young, with only 20 years since its first characterization by the pioneering studies of Raphael Mechoulam, whose discoveries conveyed these chemicals from traditional home remedies to pharmacological investigation. [4]

Since the discovery of Cannabinoid receptors, pain regulation became one of the main area of study.

Compelling evidence has shown that cannabinoids decrease allodynia both thermal and mechanical, proving their role for treating neuropathic pain. [5]


Cannabis leaf

Cannabinoids vs opioids

The main mediator of the antinociceptive effect is thought to be the cannabinoid CB1 receptor. (What is CB1, click here and what are endocannabinoids, click here)

The benefit of targeting directly CB1 receptors is endorsed by their anatomical distribution in core pain centers of the brain (Periaqueductal grey-substantia gelatinosa-medulla oblongata-dorsal horn). [6]

CB1 agonists (all the drugs that activate CB1 receptors, such as THC) prevent “wind-up” phenomenon in the dorsal horn (an exaggerated sensitization to pain leading to allodynia and hyperalgesia and hallmark of neuropathic pain).  (Hyperalgesia =increased sensation to pain, usually due to damaged pain receptors and nerve terminals)

It is hence crucial to pinpoint that manipulating cannabinoid circuitry is more advantageous than targeting directly opioids for the treatment of neuropathic pain. [6, 7] (Check out morphine for cancer and post-operative pain here)

Moreover, the medicines that activate CB1 receptors maintain their efficacy, at the opposite of morphine, which is less potent over time (so that more doses are needed, and with it, an increase in side effects).

Importantly, the spontaneous discharge (which lead to pain sensation) has been located mainly in primary afferent myelinated A-fibres, which are rich in cannabinoid receptors rather than opioids. [8]

The current medications for treating pain are still mainly opioids, but only approximately 50% of the sufferers finds relief with the available cures, thus highlighting how the clinic would greatly benefit from drugs oriented on cannabinoids modulation. [2]

On the ring today…

Boxing cage
Boxing cage: Morphine vs Cannabis

Opioids are prescribed worldwide to deal with pain.

Only recently Sativex has been approved for treatment of pain in some European Countries! If you want to know more on legalislation, click here.

Here are some facts, all the side effects for both medications.

Remember that researching cannabinoids medications does not necessarily mean using THC-based medications and lots of research is going through in this direction, making cannabinoid-based drugs even safer and non-psychoactive.

Notice that some of the effects reported for cannabis, are not “unwanted effects” by patients, such as bronchodilation, aid sleep, easing cramps, anti-inflammatory properties or antispasmodic, we report them for comparing them to Morphine.

Side effects Cannabis Morphine
  • increased heart rate
  • redness of the eyes
  • vasodilation/facial flush
  •  blood pressure changes
  • constriction of the pupil of the eye
  • irregular heart rate
  • erectile dysfunction
  • eye or eyesight problems
  • facialflushing
  • irregular heart rate
  • oedema of the extremities
  • palpitations
  • aids sleeping
  • somnolence
  • difficulty sleeping
  • sleepiness
  • aids gastrointestinal functions (diarrhea is rare)
  • anti-emetic, can cause
    nausea when overdosed
  • eases cramps
  • abdominal pain can occurr (rare)
  • biliary problems
  • constipation
  • gastrointestinal problems
  • indigestion
  • nausea
  • vomiting
  • stomachpain
  • amenorrhoea
  • decreased libido


  • anti-inflammatory
  • allergic reactions
  • anaphylactic reactions
  • itching
  • skin rash or rashes
  • worsening of pancreatitis
  • urticaria


  • muscle relaxant
  • unsteadiness
  • abnormal muscle movement
  • muscle twitching
  • confusion
  • drowsiness
  • increased appetite
  • weakness
  • euphoria
  • sense of well-being
  • depersonalization
  • hallucination
  • paranoid reaction
  • confusion
  • drowsiness
  • headaches
  • loss of appetite
  • thinking problems
  • weakness
  • convulsions
  • dysphoria-euphoria
  • fainting
  • feeling agitated
  • general feeling of being unwell
  • hallucinations
  • mood changes
  • physical dependence
  • psychological dependence
  • vertigo
  • withdrawal symptoms
  • bronchodilator
  • bronchospasm
  • pulmonary oedema
  • respiratory depression
  • dry mouth
  • severe dry mouth
  • sweating
  • renal spasms
  • urinary retention


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List of references

  1.  Scadding, J. (2003). Neuropathic Pain.ACNR. 3 (2), 8-14.
  2. Mao, J., Price, D.D., Lu, J., Keniston, L., Mayer, D.J. (2000) Two distinctive antinociceptive systems in rats with pathological pain. Neurosci. Lett., 280, 13-16.
  3. Selph, S Carson, S Fu, R et al. (2011). Drug Class Review Neuropathic Pain. Available: Last accessed 4/3/13.
  4. British Medical Association (1997) Therapeutic Uses of Cannabis. London, Harwood Academic Publishers
  5. Fox, A., Kesingland, A., Gentrym C., McNair, K., Patel, S., Urban, L., James, I. (2001) The role of central and peripheral Cannabinoid 1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain. Pain, 92, 91-100.
  6. Martin, B.R., Lichtman, A.H. (1998) Cannabinoid transmission and pain perception. Neurobiol.Dis., 5, 447-461.
  7. Lichtman, A.H., Martin, B.R. (1991) Spinal and supraspinal components of cannabinoid-induced antinociception. J.Pharmacol. Exp. Ther., 258, 517-523.

Viola Brugnatelli

Viola Brugnatelli is a Neuroscientist specialised in Cannabinoid circuitry & GPCRs signalling. Her academy and research training let her gain extensive experience on medical cannabis and terpenes both from preclinical as well as clinical perspective. In her vision, collective human knowledge behold the power for overall improvement of life, thus, it should be accessible and shareable. Viola is Founder of the science online magazine Nature Going Smart, and works as a consultant for companies & individual patients, as a speaker at seminars and workshops and as a lecturer in a CME course on Medical Cannabis in Italy, at the University of Padua.

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