What is Medicinal Cannabis?

Medicinal cannabis products are either derived from the cannabis plant (Cannabis Sativa L) or synthesized. The typical ways for patients to administer medicinal cannabis is orally or through inhalation. The most common modes of delivery are tincture, spray, capsules or vaporizers and tea.

Medicinal cannabis is administered by a prescription, as any other prescription medicine, and obtained at a pharmacy or hospital. The Danish Medicinal Agency issues approval of companies involved in medicinal cannabis production and the authorization of companies ensures consistent quality and patient safety.

Active compounds

The cannabis plant contains several compounds that are interesting for medicinal use: Cannabinoids, terpenoids, flavonoids, alkaloids. Cannabis Sativa L can be divided into different chemotypes: High CBD/low THC, high THC/low CBD, intermediate CBD and THC, low CBD and THC.
Different therapeutic indications call for different CBD:THC ratios.

Cannabinoids

Cannabinoids are currently considered the medicinally most important compound group. More than 100 cannabinoids have been identified so far, and cannabinoids has also been identified in the human body (referred to as endocannabinoids). Research indicates that the endocannabinoid system plays a role in pain perception, motoric control (movement), hunger and memory (cognitive functions).

For medicinal use, two major compounds are currently the most important: CBD (cannabidiol) and THC (Δ9-tetrahydrocannibinol).

CBD is non-psychoactive, whereas THC is known to have a psychoactive (euphoric) effect. CBD and THC have similar molecular structures but different therapeutic qualities.

Terpenoids and Flavonoids

Terpenoids are aromatic compounds that gives cannabis its distinct fragrance and flavor. Terpenoids are believed to increase blood-brain barrier permeability and contribute to cannabinoid-mediated analgesic effect. Flavonoids are believed to have several biological effects, including anti-inflammatory, anti-cancer and neuroprotective effect. A great deal of research is allocated towards mapping the biological effects of terpenes and flavonoids in combination with the effect of THC and/or CBD – often referred to as the entourage effect.

Cannabinoid Receptors

Cannabinoids are known to interact with cannabinoid CB receptors, CB1 and CB2 found in the endocannabinoid system present in all mammals. A proposed third cannabinoid receptor is GPR55 which is under the attention of researchers.

CB receptors are associated with the following effects:

  1. Psychotropic (euphoria)
  2. Antiemetic (against nausea)
  3. Analgesic (pain killer)
  4. Immunomodulation
  5. Motoric (e.g. against spasms)

These receptors are assumed to play a role in some of the cannabinoid effects, but the mechanisms are not fully known.

Receptors are found in different tissues. CB1 receptors are mainly concentrated in Central nervous system (CNS) and the majority of the CB2 receptors is found in the immune system cells and organs.

CB1

Mostly Central nervous system. Kidney, Lung, Liver

CB2

Periphery nerve terminals, Immune system cells, spleen, adipose tissue, osteo-cells

CBD, THC and Its Receptor Interactions

Even though the CBD and THC structures are similar, they have different binding affinity for the receptors. Binding affinity is a measure of how well a molecule attaches to a receptor.

THC has high affinity for- and is a partial agonist of CB1- and CB2- receptors. Many of the psychoactive THC effects are mediated by CB1 receptors. Also, the analgesic effect of THC is indicated to be due to the CB1 receptor interactions. The immunomodulatory properties of THC can be explained by the expression of the CB2 receptors in immune cells.

Pharmacological properties of THC: Immunoregulatory, anti-inflammatory, neuroprotective, anti-tumor, antiemetic (against nausea), analgesic.

CBD influences several receptors, ion channels and enzymes. CBD has a low affinity for CB1- and CB2- receptors. In presence of THC, CBD can antagonize CB1 and is thereby believed to regulate THC undesired effects (anxiety and hunger). CBD is also a negative allosteric modulator (decrease of the affinity) of the CB1 receptors and an inverse agonist (induces response opposite to the agonist) of CB2 receptors.

Pharmacological properties of CBD: immune modulating, anti-inflammatory, anticonvulsant (against spasms), antibiotic, neuroprotective, antioxidant, anxiolytic (anti-anxiety).

Clinical trials with CBS have shown a positive effect on symptom alleviation for epilepsy patients and is starting to be recognized as a long-term treatment option.

Recommended Therapeutic Areas

Based on literature search and clinical trials of therapeutic indications, the following areas are the most widely recommended relevant treatment areas with medicinal cannabis.

  • Chronical neuropathic or neurogenic pain
  • Cancer pain
  • Multiple sclerosis (CNS pain and spasmatic pain)
  • Spinal cord injury (CNS pain and painful spasticity)
  • against nausea and vomiting after chemotherapy
References
Ref noTitle, author
1Review Article: Cannabis staiva L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation and Cancer, F. Pellati, V. Borgonetti, V. Brighenti, M. Biagi, S. Benvenutti and L. Corsi
2Alexander Stephen P.H., Therapeutic potential of cannabisrelated drugs, Progress in Neuropsychopharmacology & Biological Psychiatry (2015), doi: 10.1016/j.pnpbp.2015.07.001,  PMID: 26216862
3Review Article: Systematic Review and Meta-analysis of Cannabis Treatment for Chronic Pain, Eva Martín-Sánchez, MSc, Toshiaki A. Furukawa, MD, Julian Taylor, PhD  and Jose Luis R. Martin, PhD, Pain Medicine, Volume 10, no 8, 2009
4

Guzman,M, Duarte,MJ, Blazquez,C, Ravina,J, Rosa,MC, Galve-Roperh,I, Sanchez,C, Velasco,G,

Gonzalez-Feria,L. A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br J Cancer 2006;95: 197-203

5G. Appendino, G. Chianese, O. Tagliatela-Scafati, Cannabinoids: Occurrence and Medicinal Chemistry, Current Medicinal Chemistry, 2011, 18, 1085-1099
6Turo J. Nurmikko, Mick G. Serpell, Barbara Hoggart, Peter J. Toomey, Bart J. Morlion, derek Haines,  Sativex successfully treats neuropathic pain characterized by allodynia: Arandomised, double-blind placebo-controlled clinical trial, Pain 133, 2007, 210-220
7In Danish: ”Vejledning om lægers behandling af patienter med medicinsk cannabis omfattet af forsøgsordningen”, VEJ nr 9000 21/12/2017
8

Orrin Devinsky, Chloe Verducci, Elizabeth A.Thiele, Linda C.Laux, Anup D.Patel, Francis Filloux, Jerzy P.Szaflarski, AngusWilfong, Gary D.Clark, Yong D.Park, Laurie E.Seltzer, E. Martina Bebin, Robert Flamini, Robert T.Wechsler, Daniel Friedman. Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Epilepsy & Behavior

Volume 86, September 2018, Pages 131-137

9Linda C. Laux, E. Martina Bebin, Daniel Checketts, Michael Chez, Robert Flamini, Eric D.Marsh, Ian Miller, Kathryn Nichol, Yong Park, Eric Segal, Laurie Seltzer, Jerzy P.Szaflarski, Elizabeth A.Thiele, Arie Weinstock, on behalf of CBD EAP study group. Long-term safety and efficacy of cannabidiol in children and adults with treatment resistant Lennox-Gastaut syndrome or Dravet syndrome: Expanded access program results. Epilepsy Research, Volume 154, August 2019, Pages 13-20
10In Danish:  Notat “Medicinsk brug af Cannabis”, j.nr. 2013113424 04-12-2015.
11In Danish: Dansk Lægemiddelstyrelse. Home page for Danish Medicinal Agency, about side effects of medicinal cannabis
12Ethan B Russo, REVIEW Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects, British Journal of Pharmacology, (2011) 163 1344–1364

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