17 February 2020

Weed – cannabinoids


Cannabis, marijuana, hemp, weed – these are many names for a plant, that is economically valued, feared as an (mostly) illegal drug and praised as promising medicine.

I will elucidate and summarize effects of tetrahydrocannabinol (THC) and cannabidiol (CBD) which are the two most frequent cannabinoids (ab-)used.

Photos by Add Weed, Enecta Cannabis extracts, Matteo Paganelli, GRAS GRÜN, and Matthew Brodeur on Unsplash

The plant Cannabis sativa has global distribution, though its native range is south-eastern European Russia to north-western China and Pakistan1. One reason for the global distribution is its economic use. The dried plant, often referred to as hemp for non-drug use, is high in fiber, which was historically used for threads, pipe insulation, paper making, and as biological thermal insulation2. For construction, plants have been selected to have a high fiber content. In contrast, plants used for drugs are selected for a high content in cannabinoids, especially (−)-trans-Δ⁹-tetrahydrocannabinol (THC), cannabidiol (CBD, structures below), or both of them. THC and CBD are the two most abundant cannabinoids3. While THC is responsible for the psychoactive properties favored in recreational drug (ab-)use, CBD is investigated for medicinal use3.

Chemical structure of the most abundant cannabinoids THC (left) and CBD (right).

Cannabis is the most consumed illicit drug. While there are relatively few deaths related to cannabis overdose, an increase of fatalities linked to the use of synthetic cannabinoids especially in prisons and by marginalized groups like the homeless is a matter of growing concern in Europe4. Synthetic cannabinoids often chemically refer to THC, which is the cannabinoid responsible for the high, but is also responsible for adverse effects like increased heart rate, anxiety, learning impairment, and paranoia3,5,6. In natural cannabis, adverse effects of THC are partly balanced by e.g. CBD (e.g. memory impairment, anxiety or paranoia) without affecting the high experience4.

THC is highly lipophilic and accumulated in fatty tissue. Through hydroxylation, it is converted into 11-hydroxy THC, which is the psychoactive form6. It activates cannabinoid type-1 (CB1) and type-2 (CB2) receptors in the brain to exert its psychoactive and behavioural effect5–9. Further oxidation renders THC inactive and it is excreted primarily via urine6. The euphoric state upon cannabis consumption is, most likely related to CB1 and CB2 receptors activating the dopamine reward-system5. When THC binds to the CB receptors, dopamine is released. While the amount of dopamine released is generally lower than from opioids, the release happens quicker due to cannabis being typically smoked5.

In contrast to THC, CBD has rather beneficial effects. It has anti-emetic, anti-inflammatory, anti-oxidative, and spasmolytic10. Besides offsetting the adverse effects of THC in natural cannabis, it also makes CBD interesting for medical purposes, including treatment or symptom alleviation in complex diseases like epilepsy, Alzheimer's disease, Parkinson's disease, and multiple sclerosis10.

Besides the immediate effects of cannabis constituents, a major role in its toxicity is also attributed to cannabis farming and dispose. Due to the illicit status of cannabis in most countries, use of agricultural chemicals (e.g. pesticides, heavy metals) is neither controlled nor documented3. Besides leading to toxic effects of potential residues in the product it also poses a significant environmental hazard and has to be dealt with by public authorities3.

References and further reading:

  1. Cannabis sativa L. | Plants of the World Online | Kew Science. Available at: http://www.plantsoftheworldonline.org/taxon/urn:lsid:ipni.org:names:306087-2. (Accessed: 16th February 2020)
  2. Hanf-Dämmung - ökologischer Dämmstoff. Available at: https://www.oekologisch-bauen.info/baustoffe/naturdaemmstoffe/hanf.html. (Accessed: 16th February 2020)
  3. European Monitoring Centre for Drugs and Drug Addiction & Europol. EU Drug Markets Report 2019. Publ. Off. Eur. Union, Luxemb. (2019). doi:10.2810/766585
  4. European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). European Drug Report 2019: Trends and Developments. Publ. Off. Eur. Union, Luxemb. (2019). doi:10.2810/191370
  5. WHO | The health and social effects of nonmedical cannabis use. WHO (2016).
  6. Sharma, P., Murthy, P. & Bharath, M. M. S. Chemistry, metabolism, and toxicology of cannabis: Clinical implications. Iran. J. Psychiatry 7, 149–156 (2012).
  7. Cooper, Z. D. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal. Current Psychiatry Reports 18, 1–10 (2016).
  8. Turner, A. R. & Agrawal, S. Marijuana Toxicity. StatPearls (StatPearls Publishing, 2019).
  9. Lu, H. C. & MacKie, K. An introduction to the endogenous cannabinoid system. Biological Psychiatry 79, 516–525 (2016).
  10. Millar, S. A., Stone, N. L., Yates, A. S. & O’Sullivan, S. E. A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans. Front. Pharmacol. 9, 1365 (2018).