Is cannabis good for pain relief

How and when does cannabis work?

The endocannabinoid system (ECS) controls a large number of vital functions. Sub-optimal tone of the ECS in certain regions of the nervous system is associated with disorders that are also associated with pain. The exogenous supply of cannabinoids can modulate pain and inflammation processes. Studies have shown minor to moderate pain relieving effects, and in individual cases major pain relievers for various types of chronic pain. Individuals with chronic neuropathic pain and symptoms of stress seem to benefit particularly.

A well-integrated 60-year-old man presents with painful spastic cramps in his legs and arms that occur primarily at night and which are attributed to an immune-mediated neuropathy. As a result, massively disturbed night sleep. Basic therapy with rituximab and immunoglobulins. In the past, good effect under Flupirtin retard 400 mg, which was withdrawn from the market in 2018 due to liver toxicity. No relief with gabapentin, pregabalin, amitriptyline, and mirtazapine. With opioids (tilidine, hydromorphone) no effect and increase in sleep disorders. L-Dopa without affecting the symptoms. Prescription of dronabinol after cost approval by the payer. After titrating up to 5 mg at night, there was a clear decrease in nocturnal pain and a relevant improvement in night sleep. However, this leads to diarrhea and a tendency to nausea. For this reason, switch to an oral cannabis full extract (THC10: CBD10 10 mg / ml). In the dose of 10 mg at night, a very good therapeutic result without side effects is achieved. The previously used (inactive) substances mirtazapine and gabapentin could be completely discontinued.

The ECS is composed of specific cannabinoid receptors (CB1, CB2) and endogenous ligands. Receptor-dependent and receptor-independent effects that can contribute to pain relief are [1]:
  • Reduction of nociceptive transmission
  • Anti-inflammation, anti-fibrosis
  • Activation of pain inhibitors
  • Reduction of the central stress response
  • Initiation of anti-hyperalgesic mechanisms

It is important to understand that inflammatory and psychological factors play an extremely important role in chronic pain.

What about the effectiveness?

In a very heterogeneous group of randomized controlled studies, which include data from approx. 2,500 patients, cannabinoids and cannabis flowers have a low to moderate, sometimes also high effectiveness in chronic pain, usually as an additional medication to other active ingredients [1, 5]. Meta-analyzes of these studies questioned the effectiveness of cannabinoids in chronic pain, which is particularly in contradiction with information from observational studies [5]. Possible reasons for the low external evidence from meta-analyzes are [1, 5, 6]:
  • the strong clinical heterogeneity of the studies,
  • Errors in the statistical processing of the data,
  • using different cannabinoids and dosages,
  • the short duration of the studies,
  • the complexity of pain patients,
  • the use of incorrect outcome parameters.

It has long been known that cannabinoids tend to improve the negative affects, symptoms of tension and sleep disorders associated with chronic pain and have less direct influence on pain intensity [5, 7]. For this reason, it is understandable that neuropathic pain in particular responds to cannabinoids, as this type of pain "annoys" those affected in a special way, e.g. B. by the fact that they also occur at rest. In addition, these relationships also explain why those chronic pain patients who are most likely to benefit from cannabinoids are those who are severely "stressed", mostly due to the chronic pain itself, but also due to pre-existing or co-existing psychosocial factors. From a cross-sectional survey [15] it is estimated that around two to three million people in Germany are also under great psychological stress at the same time as chronic pain. "Fibromyalgia Syndrome" and "Chronic Pain Disorder" with somatic and psychological factors are the most frequently used ICD-10 codes.

Since 2005, the Federal Opium Agency has been able to issue individual exceptional permits for the acquisition of cannabis flowers or cannabis extracts on the basis of Section 3, Paragraph 2 of the Narcotics Act (BtMG) at the request of treating physicians [3]. In contrast to this, the semi-synthetically produced THC (dronabinol), which has been prescribable since 1998, can be prescribed on a narcotic drug prescription so that the costs incurred can also be covered by the statutory health insurance (GKV). According to the so-called "Nikolaus decision" of the Federal Constitutional Court on December 6, 2005, the statutory health insurance scheme's obligation to assume the costs was accepted in particular [4] if
  • "there is a not entirely remote prospect of a noticeable positive effect (on the course of the disease)".
In the law "Cannabis as Medicine", Section 31, Paragraph 6, SGB V, which came into force on March 10, 2017, and which replaced the regulation of individual exceptional permits, it was also stipulated that the prerequisite for the assumption of costs by the GKV can then be considered fulfilled, if
  • a generally recognized service corresponding to the medical standard is not available or cannot be used in individual cases after weighing the expected side effects and taking into account the state of the disease
  • there is a serious illness that is life-threatening or has a lasting effect on the quality of life.

70% of patients with chronic pain are cared for by general practitioners, 27% by orthopedic surgeons and only 2% by pain therapists [8]. Around every fifth patient in general practitioners' practices complains of chronic pain [9]. Back and joint pain are very common, as are the comorbidities of anxiety, depression, somatization and post-traumatic stress disorder. Organ findings and the extent of the complained of impairments often do not correlate [9]. If there are no immediately treatable organ disorders or if the functional pain share is very high, the aim of the treatment is functional restoration (not primarily pain reduction). Medicines, in some cases also cannabinoids and cannabis flowers (Table 1), can contribute to functional restoration in the sense of a bridging and supportive function.

When it comes to the question of whether cannabinoids can be used, the following questions are of the greatest importance, resulting in a structured approach:
  • What is the role of structural damage in the development and maintenance of pain?
  • What is the percentage of nerve pain?
  • How badly is the patient psychologically stressed, is there trauma, is there a post-traumatic stress disorder?
  • Which therapeutic approaches have been tried so far?
  • Is pain therapy integrated into an overall concept (psychotherapeutic and physiotherapeutic procedures)?
When it comes to the question of which cannabinoid is used, the following procedure is recommended:
  • Primarily oral cannabinoid (dronabinol, cannabis whole extract).
  • Always start with the smallest dosage (e.g. 0.5 to 1 mg THC per day).
  • Only very slow increase in dose (e.g. increase by 1 mg per week).
  • Stick to low daily doses (e.g. 5 to 10 mg per day).
  • One to a maximum of three doses per 24 hours.

The procedure mentioned corresponds to clinical experience that the duration of action of orally given cannabinoids can be very long - active metabolic products probably play a role here - and low doses are usually sufficient. In this way, the occurrence of side effects (Table 2) can largely be avoided. If cannabinoid therapy is started, it is not necessary to discontinue the previous medication. If the patient responds to the cannabinoid, an attempt can be made to change the existing medication (in particular reducing the doses of opioids).

If patients imagine who have inhaled cannabis flowers as a self-medication, the use of oral or oromucosal administration should always be advocated, as there is also lung strain with vaporization and the pharmacokinetics are unfavorable due to high peak levels and short action times. The effects of inhalation increase the risk of developing addiction. When using the oromucosal mouth spray, make sure that the starting dose (1 stroke) already corresponds to a dose of 2.7 mg THC and that up to 20% of users can damage the mucous membrane in the mouth area. An advantage of inhalation can be the quick effect in acute events (e.g. migraine attacks) and the lower accumulation of 11-OH-THC, which is considered to be more psychoactive compared to THC. Cannabinoid and terpene compositions can differ in the cannabis plants, so that there is an individually different effect-side effect profile [2]. Increased effectiveness and reduction of side effects with full extracts and cannabis flowers are referred to as the entourage effect.

As with any other drug that works in the CNS area, driving ability can be impaired. Communication about this should be documented by the patient's signature. Here, too, cannabinoid therapy taken orally - after time intervals - has advantages.

We are working on cannabinoids that do not enter the central nervous system and that have antifibrosis, anti-inflammatory and analgesic effects [10, 11].

1. Karst M. Cannabinoids in pain medicine. Pain 2018; 32: 381-396.
2. Russo EB, Marcu J. Cannabis pharmacology: the usual suspects and a few promising leads. Adv Pharmacol 2017; 80: 67-134.
3. Rätsch C. Hemp as a remedy. Aarau, AT Verlag 1998: 10 to 21.
4. Ransomware JJ. "Anslingerian" politics: the history of anti-marijuana sentiment in federal law and how Harry Anslinger`s anti-marijuana politics continue to prevent the FDA and other medical experts from studying marijuana`s medical utility. Food and Drug Law 1999., last accessed on February 17, 2018.
5. Mechoulam R, Shvo Y. The structure of cannabidiol. Tetrahedron 1963; 19: 2073-2078.
6. Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish J Amer Chem Soc 1964; 86: 1646-1647.
7. McPartland JM, Pruitt P. Sourcing the code: Searching for the evolutionary origins of cannabinoid receptors, vanilloid receptors, and anandamide. J Cannabis Therapeutics 2002; 2 (1): 73-103.
8. Akerblom S, Perrin S, Rivano Fischer M, McCracken LM. The impact of PTSD on functioning in patients seeking treatment for chronic pain and validation of the posttraumatic diagnostic scale. Int J Behav Med 2017; 24 (2): 249-259.
9. Grotenhermen F, Häussermann K. Cannabis. Prescription aid for doctors. Stuttgart, Wissenschaftliche Verlagsgesellschaft mbH 2017.
12. Campbell G, Stockings E, Nielsen S. Understanding the evidence for medical cannabis and cannabis-based medicines for the treatment of chronic non-cancer pain. Eur Arch Psychiatry Clin Neurosci 2019; 269 (1): 135-144.
13. Karst M, Passie T. Considerable heterogeneity. Dtsch Arztebl Int 2018; 115 (9): 143
14. Karst M, Wippermann S, Ahrens J Role of cannabinoids in the treatment of pain and (painful) spasticity. Drugs 2010; 70 (18): 2409-2438.
15. Haus W, Schmutzer G, Henningsen P, Brähler E. Chronic pain, pain illness and satisfaction of those affected with pain treatment in Germany. Results of a representative sample of the population. Pain 2014; 28: 83-492.
16. Dietl M, Korczak D. Care situation in pain therapy in Germany in an international comparison with regard to over, under or incorrect care. Health Technology Assessment 2011 series; Volume 111.
17., last accessed on 02.03.2019.
18. Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. JAMA 2003; 290 (13): 1757-1762.
19., last accessed on 02.03.2019.

Doctor for anesthesiology, special pain therapy, psychotherapy, acupuncture, palliative medicine. Clinic for Anaesthesiology and Intensive Care Medicine, Pain Clinic, Hannover Medical School

Conflicts of Interest: M. Karst has received lecture fees from Bionorica Ethics GmbH.

More posts on similar topics: