This Risks Associated With Synthetic Cannabinoids

The food and drug market is full of products that are almost the same, but actually have major differences in terms of health, safety, and long term side effects. Coke and Diet Coke’s flavors are nearly identical, but Diet Coke’s sweetener, aspartame, can cause cancer in high doses. [1] When cooking, olive oil might seem like it’s interchangeable with other vegetable oils, but the benefits of extra virgin olive oil put it in another category entirely. [2] 

Over the last few decades, the rising popularity of synthetic cannabinoids is proving to be another example of this. [3] Users may not notice a difference between organic and synthetic cannabinoids, but that does not mean they are the same.

Cannabis use has been documented for thousands of years, and the potential therapeutic effects are well known. [4] With synthetic cannabinoids, this is not the case. The two share a lot of common side effects, but the ones exclusive to the synthetics can be alarming, and may have short and long term consequences. 

Psychological Effects

The effects of cannabis are not the same for everyone. Some users describe experiences that are mild and comforting, while others find that cannabinoids can increase paranoia and anxiety. With this in mind, there are certain psychological changes that are more common than others.

One of these feelings is the idea that space or time may distort when using cannabis. [5] This is something that users of both synthetic and biological cannabinoids users may experience, and it’s pretty mild compared to the possibility of paranoia or psychosis. [6][7] These more dramatic side effects are also possible with both types of cannabinoids, but they are a lot less common. 

There is a noticeable difference with synthetic cannabinoids compared to the natural ones. Take, for example, the most severe psychological change: psychosis, or a disconnection from reality. With organic cannabis, it is only certain, predisposed people who fall victim to this, and in most cases it is not something the average user has to worry about. [8]

 With synthetic cannabinoids, though, psychosis seems to occur more often, and some evidence indicates that there may be a stronger causation relation between the two. [9] Meaning, synthetic cannabinoid users have a higher likelihood of developing major psychological problems compared to those who stick to the plant derived cannabinoids..

Changes in Mood

Mood changes are also common for cannabinoid users. For many, this change can be a positive one, where cannabis actually elevates their mood. For others, this is not necessarily the case. There are certain people, particularly new or inexperienced users, who may experience panic attacks or increased anxiety after using it. [6] This can also happen with long term users, but the anxiety or other mood disorders they feel are a lot less noticeable and is more of a general feeling of foreboding. [10] 

Synthetic cannabinoids can also make users feel anxious or generally nervous, but they also have been linked to thoughts of suicide in the short term, and increased instances of depression and persistent anxiety in the long term. [11][12] 

Anxiety and these mood disorders are already a big downside to cannabis use, but thoughts of self harm or depression are major causes for concern. This is something that synthetic cannabinoid users should take very seriously, and recognize that this may be the source of their newly negative moods, anxiety, or dark thoughts.

Memory and Cognitive Functions

Cannabis’s negative association with memory, attention, and cognitive functions have been well documented. [13] This is another side effect that can affect different people in different ways, but many cannabis users find these side effects to be relatively minor, and are still able to function to a relatively normal degree. These changes can occur both in the short and long term, but there are additional possibilities for long term users. 

Prolonged cannabis use can sometimes lead to difficulty with verbal learning or the ability to multitask. [14] All in all, these changes may not be that much worse than someone who develops dementia later in life, though. For synthetic cannabinoid users, on the other hand, the effects on memory and cognitive function can be a lot more severe.

Some users report significant memory impairment, even going as far as reporting amnesia or blackouts. [15] Forgetting where you put your keys is bad, but losing whole segments of time could be really consequential. The same is also true when considering long term use of synthetic cannabinoids on cognitive functions. There is not very much data available to confirm this, but if the short term consequences are more extreme, the theory is that the long term use will lead to bigger problems with memory and attention as well. 

Effects on Brain Structure and the Nervous System

Addressing psychological, mood, and memory functions are all related to the brain, and the explanation for why these two types of cannabinoids have different effects may be as simple as looking at where they work in the brain. Organic cannabis has been linked to changes in the hippocampus and amygdala. [16] This may sound complex, but these parts of the brain are responsible for regulating mood and memory, which explains the previously listed issues. 

This is pretty minor compared to the parts of the brain that synthetic cannabinoids work on. The evidence is still limited, but synthetic cannabinoids appear to alter gray matter, which can affect memory, but also deals with emotion and muscular movements throughout the body. [17]

This explains the similar issues with memory, but it could also explain the increased risk of suicidal thoughts, depression, and anxiety. But what about muscular control? Studies show that the biggest risk to the nervous system from synthetic cannabinoids is an increased possibility of seizures and muscle spasms. [18] This is not to say that cannabis doesn’t also impact the nervous system, but not all of its side effects are negative.

With natural cannabis, it is possible to experience symptoms like dizziness or muscular tension, but other cannabinoids have been prescribed to treat neurological disorders like epilepsy or Parkinson’s disease. [19][20] These symptoms are at worst unpleasant, and at best may provide much needed relief. Compared to the potential to lose control of your body, the risks that synthetic cannabinoids pose are not even close.

Changes in the Cardiovascular System

Moving on from the brain and cognitive functions, it’s also worth looking at how these two types of cannabinoids can affect the rest of the body. When looking at the cardiovascular system, it is possible for natural cannabinoids to increase the heart rate for some users. [21] In the short term, this may provide some discomfort, and it could lead to a higher likelihood of cardiovascular diseases, especially compared to people who don’t use cannabis at all. [22] 

These long term risks are also true for synthetic cannabinoids, but there are also several more short term concerns that users should be aware of. These risks include heart rates rising above 100 beats per minute, high blood pressure, heart attacks, irregular heartbeats, and chest pain or palpitations. [23] When considering these risks to the cardiovascular system, it may be the case that fewer synthetic cannabinoid users last long enough to experience the long term ones.

Other Parts of the Body

Depending on how users consume cannabis, it is possible that their lungs or digestive systems could face long term effects too. [24][25] Synthetic cannabinoids can also affect these areas, but there are also studies suggesting they can also harm users’ kidneys, eyes, and may cause severe muscular decline. [26][27][28] If all of these side effects weren’t disturbing enough, maybe the most alarming is the potential for users to develop dependence issues, withdrawal, or death when using synthetic cannabinoids. [29] 

Natural cannabinoids can also be habit-forming, but the physical side effects from quitting are almost nonexistent. It is also true that there has never been a recorded case of death by overdosing on plant derived cannabinoids. With synthetic cannabinoids, neither of these are true, and when tallying up all the risks associated with their usage, it is clear that while these two sources of cannabinoids may produce similar experiences for their users, they are remarkably different from each other.

References:

1. Landrigan, Philip J., and Kurt Straif. “Aspartame and cancer–new evidence for causation.” Environmental Health 20 (2021): 1-5.
2. Beneito-Cambra, Miriam, et al. “Direct analysis of olive oil and other vegetable oils by mass spectrometry: A review.” TrAC Trends in Analytical Chemistry 132 (2020): 116046.
3. Scourfield, Andrew, et al. “Synthetic cannabinoid availability on darknet drug markets—changes during 2016–2017.” Toxicology Communications 3.1 (2019): 7-15.
4. MacCallum, Caroline A., Lindsay A. Lo, and Michael Boivin. ““Is medical cannabis safe for my patients?” A practical review of cannabis safety considerations.” European Journal of Internal Medicine 89 (2021): 10-18.
5. Ashton, C. Heather. “Pharmacology and effects of cannabis: a brief review.” The British Journal of Psychiatry 178.2 (2001): 101-106.
6. Hall, Wayne, and Louisa Degenhardt. “Adverse health effects of non-medical cannabis use.” The Lancet 374.9698 (2009): 1383-1391.
7. Volkow, Nora D., et al. “Effects of cannabis use on human behavior, including cognition, motivation, and psychosis: a review.” JAMA psychiatry 73.3 (2016): 292-297.
8. Di Forti, Marta, et al. “Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study.” The Lancet Psychiatry 2.3 (2015): 233-238.
9. Fattore, Liana. “Synthetic cannabinoids—further evidence supporting the relationship between cannabinoids and psychosis.” Biological psychiatry 79.7 (2016): 539-548.
10. Crippa, José Alexandre, et al. “Cannabis and anxiety: a critical review of the evidence.” Human Psychopharmacology: Clinical and Experimental 24.7 (2009): 515-523.
11. Castaneto, Marisol S., et al. “Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications.” Drug and alcohol dependence 144 (2014): 12-41.
12. Castellanos, Daniel, et al. “Synthetic cannabinoid use: a case series of adolescents.” Journal of Adolescent Health 49.4 (2011): 347-349.
13. Curran, Valerie H., et al. “Cognitive and subjective dose-response effects of acute oral Δ 9-tetrahydrocannabinol (THC) in infrequent cannabis users.” Psychopharmacology 164 (2002): 61-70.
14. Pope, Harrison G., et al. “Neuropsychological performance in long-term cannabis users.” Archives of general psychiatry 58.10 (2001): 909-915.
15. Spaderna, Max, Peter H. Addy, and Deepak Cyril D’Souza. “Spicing things up: synthetic cannabinoids.” Psychopharmacology 228 (2013): 525-540.
16. Batalla, Albert, et al. “Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings.” PloS one 8.2 (2013): e55821.
17. Nurmedov, Serdar, et al. “Thalamic and cerebellar gray matter volume reduction in synthetic cannabinoids users.” European Addiction Research 21.6 (2015): 315-320.
18. Ortiz, Yuma T., Lance R. McMahon, and Jenny L. Wilkerson. “Medicinal cannabis and central nervous system disorders.” Frontiers in Pharmacology 13 (2022): 881810.
19. Iannotti, Fabio Arturo. “Cannabinoids, Endocannabinoids, and Synthetic Cannabimimetic Molecules in Neuromuscular Disorders.” International Journal of Molecular Sciences 25.1 (2023): 238.
20. Chayasirisobhon, Sirichai. “Cannabis and neuropsychiatric disorders: an updated review.” Acta Neurol Taiwan 28.2 (2019): 27-39.
21. Goyal, Hemant, Hamza H. Awad, and Jalal K. Ghali. “Role of cannabis in cardiovascular disorders.” Journal of thoracic disease 9.7 (2017): 2079.
22. Reece, Albert Stuart, Amanda Norman, and Gary Kenneth Hulse. “Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: a longitudinal study.” BMJ open 6.11 (2016).
23. Pacher, Pal, et al. “Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly.” Nature Reviews Cardiology 15.3 (2018): 151-166.
24. Tetrault, Jeanette M., et al. “Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review.” Archives of internal medicine 167.3 (2007): 221-228.
25. Cohen, Lawrence, and Manuela G. Neuman. “Cannabis and the gastrointestinal tract.” Journal of Pharmacy & Pharmaceutical Sciences 23 (2020): 301-313.
26. D’Errico, Stefano, et al. “Acute kidney injury (aki) in young synthetic cannabinoids abusers.” Biomedicines 10.8 (2022): 1936.
27. Bilici, Rabia. “Synthetic cannabinoids.” Northern clinics of Istanbul 1.2 (2014): 121.
28. Zhao, Aiyu, et al. “Rhabdomyolysis and acute kidney injury requiring dialysis as a result of concomitant use of atypical neuroleptics and synthetic cannabinoids.” Case reports in nephrology 2015 (2015).
29. Van Hout, Marie Claire, and Evelyn Hearne. “User experiences of development of dependence on the synthetic cannabinoids, 5f-AKB48 and 5F-PB-22, and subsequent withdrawal syndromes.” International Journal of Mental Health and Addiction 15 (2017): 565-579.