Synthetic Marijuana: The Dangerous Synthetic Cannabinoids

Hello everyone, good morning, good afternoon, good evening, or good night, wherever you are. What is this synthetic marijuana, you may ask. Well, synthetic cannabinoids are a type of compounds that mimic the effect of marijuana, produced in laboratories. They were initially developed to medicinal use.

However, and very unfortunately, synthetic marijuana refers, more specifically, to a type of illegal drug, very harmful to health, and which bears no resemblance to the plant’s natural cannabinoids. Today I want to tell you about this very interesting subject, which I learned about in order to write this text.

Where does synthetic marijuana come from?

Types of cannabinoids

As you may already know, cannabinoids are chemical compounds of diverse origin [1].

Cannabinoids that are produced by the body are called endocannabinoids, and one example is anandamide. On the other hand, phytocannabinoids are produced by plants, especially marijuana, and one example is CBD or cannabidiol.

Where do synthetic cannabinoids come from?

There are also synthetic cannabinoids, produced under laboratory conditions. It is said that these synthetic cannabinoids were initially developed therapeutically [1].

Although synthetic cannabinoids were apparently produced for medical purposes, they have a high potential for abuse, especially in young people.

Colloquially, synthetic cannabinoids are called synthetic marijuana because they can look like dried grass and act on the endocannabinoid system. Although, as we will see, they have nothing to do with the compounds produced by cannabis.

What is synthetic marijuana?

Synthetic marijuana, also known as spice or K2, is a type of drug that is created in a laboratory.

These synthetic cannabinoids, misnamed synthetic marijuana, are of great public health concern because of their high and unpredictable toxicity, their high potential for abuse particularly by youth, and their high rate of use [3]. Apparently, the use of synthetic cannabinoids is twice as high in young men than in young women [4].

What does synthetic marijuana look like?

Its appearance can be powder, liquid or dry grass (because it is sprayed on the grass). It is sold with more potent effects than marijuana, and can be smoked, vaped or ingested.

Why are they called synthetic cannabinoids, if they do not resemble cannabis?

Synthetic marijuana has a different chemical structure to the cannabinoids found in the plant Cannabis sativa .

Why is it called synthetic marijuana?

The reason they are called synthetic cannabinoids is because the drug acts on the endocannabinoid system, just like marijuana, although its effects are dangerous compared to the effects of weed.

Synthetic marijuana is a synthetic cannabinoid drug that acts on the endocannabinoid system.

Technically, the definition of cannabinoids are those substances that interact with our endocannabinoid system. For this reason, synthetic marijuana is classified as a cannabinoid, although it does not resemble the plant compounds we are all familiar with.

The endocannabinoid system is associated with many physiological functions, such as cognitive and behavioral processes, motor control, pain, appetite, cardiovascular parameters, cardiovascular motility, and immune regulation among many other processes [1].

The endocannabinoid system is composed of CB1 and CB2 cannabinoid receptors and cannabinoid enzymes [2].

History of cannabinoid synthesis

In the 1960s, Professor Raphael Mechoulam and his collaborators isolated and then synthesized under laboratory conditions the phytocannabinoid THC (delta-9-tetrahydrocannabinol), present in the marijuana plant [5].

Although the marijuana plant produces them in an acidic form (THCA), I will refer to these cannabinoids in their neutral form (THC). Thanks to this work, the human body’s cannabinoid receptors CB1 and CB2 were identified.

THC was identified as a partial agonist of these receptors [5]. An agonist is a molecule that activates the receptor, i.e. it causes the receptor to produce a biological response.

CBD and THC have opposite effects on the human body

CBD or cannabidiol, another phytocannabinoid from the Cannabis sativa plant, acts differently from THC. Apparently, CBD does not have a direct effect on CB1 and CB2 receptors, but acts on other receptors, such as serotonergic receptors [6].

But CBD does antagonize CB1 and CB2 receptors in vitro [7]. An antagonist of these receptors stops, attenuates or prevents the effect of endocannabinoids. In addition, CBD regulates the unpleasant effects of THC, such as anxiety [8].

Synthetic cannabinoids for therapeutic use

Based on Mechoulam’s findings, prescriptions were developed from synthesizing THC under laboratory conditions, such as the drugs Dronabinol (Marinol®, Syndros®) and Cesamet (nabilone) [5].

And, although these drugs are used therapeutically, many also have adverse effects [5], similar to those produced by the synthetic cannabinoids I will mention below.

Yet, they also have therapeutic possibilities, at least in animal studies, which have found that they can treat diseases such as cancer, pain, and inflammation, among others [5]. It has also been reported that patients with anorexia treated with Dronabinol gained weight without major psychoactive effects [9].

Synthetic cannabinoids for medical use can also have adverse effects, similar to those sold on the illegal market.

Methods to synthesize CB1 and CB2 receptor agonists were used by chemists, who clandestinely started to produce synthetic cannabinoids for illicit purposes [5].

What are the effects of synthetic marijuana?

Types of synthetic cannabinoids

There are several types of synthetic cannabinoids, also known as synthetic marijuana or synthetic cannabis.

What are the differences between the effect of natural and synthetic cannabinoids?

As I mentioned above, both phytocannabinoids such as THC and synthetic cannabinoids stimulate the same CB1 and CB2 receptors. But, synthetic cannabinoids are associated with high rates of toxicity and hospitalizations compared to natural marijuana [3].

This is because synthetic cannabinoids are direct agonists of cannabinoid receptors [3], and have an affinity four to five times higher than that of THC [10], which is a partial agonist [3].

Unlike THC which is a partial agonist, synthetic cannabinoids are direct agonists of endocannabinoid receptors.

In addition, these synthetic cannabinoids act unpredictably. Products containing them and sold on the illicit market may also contain other contaminants [3].

What is the chemical structure of synthetic marijuana?

The chemistry of cannabinoids

Cannabinoids (agonists or antagonists of endocannabinoid receptors) are a diverse group of liposoluble (fat-soluble), non-polar and volatile compounds. They are composed of a structure of 22 to 26 carbon atoms, and are characterized by a structural chain of four to nine saturated carbons [11].

What is the chemical composition of synthetic cannabinoids?

The chemical composition of the synthetic cannabinoid molecule has a main center of aromatic structure (benzene-based hydrocarbons) linked to a second portion, which can be an alkyl chain (functional group containing only carbons and hydrogens), linked by carbons [1].

The structure of synthetic cannabinoids is not related to that of phytocannabinoids, although both have a two-cycle conformation [11].

The chemical structure of synthetic cannabinoids is not related to that of phytocannabinoids such as THC.

These synthetic cannabinoids have different chemical groupings, such as naphthoylindoles, benzoylindoles, phenylacetylindoles, adamantylindoles, cyclophenols and various other groups [10].

Adverse effects of synthetic marijuana use

What is the effect of taking synthetic marijuana?

Like phytocannabinoids, synthetic cannabis can be smoked, ingested or vaporized, and also has psychoactive effects [3].

Several medical anomalies have been reported when consuming synthetic cannabinoids, popularly called synthetic marijuana. These include tachycardia, agitation, dizziness, hallucinations, hypertension, paranoia, convulsions, nausea, confusion, vertigo, irritability, slurred speech, and chest pain [3, 10].

Other serious medical consequences of synthetic marijuana use have included renal, gastrointestinal, and cardiovascular injuries [3].

Synthetic marijuana use can lead to serious health problems, such as kidney damage and gastrointestinal and cardiovascular complications.

Types of synthetic marijuana

One of the best known synthetic cannabinoids is ADB-PINACA, which, as I have previously described, has caused kidney disease [5]. In mice, this synthetic cannabinoid produced seizures [12]. Also spice or k2.

What does synthetic marijuana look like?

Synthetic marijuana products are promoted with names such as incense, fragrance and potpourri.

These products look like natural dried marijuana flower already ground, at least in the photos I saw [13].

These synthetic cannabinoids are sprayed on already ground and dried flower for smoking, and are also sold in liquid form for vaporization or inhalation in electronic cigarettes [14].

Well, after studying about synthetic cannabinoids and the serious consequences that the consumption of synthetic marijuana can have, I wonder: If we have such a special plant that produces so many compounds, why put our health at risk with these synthetic cannabinoids? Isn’t it enough with those natural compounds produced by the cannabis plant, which can also bring us medical benefits, and that we can literally grow in the closet, in the shower or in the basement?

I hope you enjoyed learning about synthetic marijuana as much as I did and that you were as scared as I was. I strongly encourage you not to take any drugs of this type.

  

Referencias

1. Le Boisselier, R., et al, Focus on cannabinoids and synthetic cannabinoids. Clinical Pharmacology & Therapeutics, 2017. 101(2): p. 220-229.

Iversen, L., Cannabis and the brain. Brain, 2003. 126(6): p. 1252-1270.

Mills, B., A. Yepes, and K. Nugent, Synthetic cannabinoids. The American journal of the medical sciences, 2015. 350(1): p. 59-62.

4. Vidourek, R.A., K.A. King, and M.L. Burbage, Reasons for synthetic THC use among college students. Journal of Drug Education, 2013. 43(4): p. 353-363.

5. Sholler, D.J., et al., Therapeutic potential and safety considerations for the clinical use of synthetic cannabinoids. Pharmacology Biochemistry and Behavior, 2020. 199: p. 173059.

6. Papaseit, E., et al., Cannabinoids: from pot to lab. International journal of medical sciences, 2018. 15(12): p. 1286.

7. Leo, A., E. Russo, and M. Elia, Cannabidiol and epilepsy: rationale and therapeutic potential. Pharmacological research, 2016. 107: p. 85-92.

8. Rog, D.J., Cannabis-based medicines in multiple sclerosis-a review of clinical studies. Immunobiology, 2010. 215(8): p. 658-672.

9. Andries, A., et al., Dronabinol in severe, enduring anorexia nervosa: a randomized controlled trial. International Journal of Eating Disorders, 2014. 47(1): p. 18-23.

10. ElSohly, M.A., et al., Synthetic cannabinoids: analysis and metabolites. Life sciences, 2014. 97(1): p. 78-90.

11. Hudson, S. and J. Ramsey, The emergence and analysis of synthetic cannabinoids. Drug testing and analysis, 2011. 3(7-8): p. 466-478.

12. Wilson, C.D., F. Zheng, and W.E. Fantegrossi, Convulsant doses of abused synthetic cannabinoid receptor agonists AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA and JWH-018 do not elicit electroencephalographic (EEG) seizures in male mice. Psychopharmacology, 2022. 239(10): p. 3237-3248.

13. Spaderna, M., P.H. Addy, and D.C. D’Souza, Spicing things up: synthetic cannabinoids. Psychopharmacology, 2013. 228: p. 525-540.

14. Abuse, N.I.o.D., Synthetic cannabinoids (K2/spice) DrugFacts. 2018. Consultation: March 1, 2023.

Information on synthetic marijuana (frequently asked questions)

What are the side effects of synthetic marijuana?

Synthetic marijuana also has psychoactive effects, but its use can lead to serious health problems related to kidney and heart damage, among others. Side effects of synthetic marijuana use include tachycardia, agitation, dizziness, hallucinations, hypertension, paranoia, convulsions, nausea, confusion, vertigo, irritability, slurred speech and chest pain.

Who uses synthetic marijuana?

Synthetic marijuana use occurs mainly among young men, and mostly in the United States and Europe.

Where does synthetic marijuana work?

Synthetic cannabinoids act on the endocannabinoid receptors CB1 and CB2, as do cannabinoids produced by the plant (phytocannabinoids) or those produced by the human body (endocannabinoids).

What are the uses of synthetic marijuana?

Although synthetic cannabinoids or synthetic marijuana are used illicitly, there are drugs for therapeutic use based on synthetic cannabinoids, such as Marinol and Cesamet.

How is synthetic marijuana produced?

Synthetic marijuana is generally produced in the laboratory by chemists who know the structure of cannabinoid receptors, where these molecules act in the human body.

Dra. Daniela Vergara
Investigadora y catedrática | Especialista en cultivos emergentes y consultora de cannabis

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