Motivation and emotion/Book/2021/Synthetic cannabinoids and emotion
What are the emotional effects of synthetic cannabinoids?
Overview
editSynthetic cannabinoids are psychoactive chemicals that interact with cannabinoid receptors in the brain and central nervous system (CNS), altering neurotransmitter activity (Alexandre et al., 2020). This chapter aims to understand the role of synthetic cannabinoids on neuronal functioning to explain the emotional and physical impact of consumption. Current research has determined that synthetic cannabinoids produce more adverse effects than natural cannabinoids due to the higher binding affinity and full-agonist activity toward the Cannabinoid-1 (CB1) and Cannabinoid-2 receptors (CB2) (Sutcliffe & Ralphs, 2018; Wells et al., 2011). The impact of consumption of synthetic cannabis will be discussed, including acute versus chronic intoxication, and outlining the psychical, behavioural, cognitive, and psychosocial symptoms.
Focus questions:
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History and Prevalence of Synthetic Cannabinoids
edit- The first synthetic cannabinoid was developed by the organic chemist John Huffman of Clemson University in 2008. The active ingredient in synthetic cannabis is JWH-o18, a naphthoylindole, belonging to the aminoalkylindole family, which are cannabinergic compounds that pose as cannabinoid receptor agonists. Despite JWH-o18 having a different chemical structure to Tetrahydrocannabinol (THC), the effects are similar (Byard & Payne-James, 2015).
- Production of synthetic cannabinoids begins on a large scale in China. A bulk powder is produced via simple chemical reactions using legal substances (Sutcliffe & Ralphs, 2018). The bulk powder is then shipped to Europe and mixed or sprayed onto dried plant material that does not contain tobacco or cannabis. The material is dried and packaged as an air freshener, incense, or a smoking mix, and is distributed to other countries including America and England to sell (Sutcliffe & Ralphs, 2018).
- Synthetic cannabis is legally sold in many countries and is available to purchase online or in head shops (Cottencin et al., 2014).
- Synthetic cannabinoids are known as K2 or Spice but have many other names (Sutcliffe & Ralphs, 2018). Similarly, synthetic cannabis has many different chemical formulations - the contents are unknown (Wells et al., 2011), this causes unpredictable reactions after intoxication due to the varying potential toxicity (Millis et al., 2018).
- Synthetic cannabinoid products first appeared on the internet for sale in 2006. Popularity began in 2008 when a German reporter announced that Spice had a similar high to natural marijuana but did not appear in drug tests (Sutcliffe & Ralphs, 2018). The unpredictability of synthetic cannabinoids combined with the inability to be detected in urine drug tests pose a large public health concern (Millis et al., 2018).
Synthetic Cannabinoids and Short Term Impacts
editAcute intoxication of synthetic cannabinoids can cause users to experience both positive and negative effects due to the varying binding affinity to the CB1 and CB2 receptors (Wells et al., 2011).
Case Study Part 1: Short Term Effects, Acute Intoxication and Hangover
Lana first tried synthetic marijuana at the age of 17. She brought it under the name “Spice”, her dealer told her it was natural weed. Lana met with a friend and smoked a joint, having a good time, she felt happy and relaxed. The next day Lana experienced a low mood accompanied by headaches and feeling disconnected from reality (Soussan et al., 2014). |
Description of Synthetic Cannabinoids:
edit- Synthetic cannabinoids such as JWH-018 mimic the effect of THC (the main psychoactive component of cannabis) (Sutcliffe & Ralphs, 2018), Lana's acute intoxication caused her to experience positive and happy feelings. This euphoric effect caused by synthetic cannabis is common as the chemical structure of JWH-018 produces similar effects to natural marijuana (THC) (Wells et al., 2011). Despite Lana's positive experience, acute intoxication of synthetic cannabis can also cause users to experience fear, paranoia, nausea and dizziness, respiratory difficulties, and tachycardia (Akram et al., 2019).
Neurology
edit- JWH-018 is the most common synthetic cannabinoid compound found in Spice and K2. Synthetic cannabis is abused due to the full-agonist activity to the CB1 and CB2 receptors (Wells et al., 2011). Synthetic cannabinoids have a higher affinity for the CB1 and CB2 receptors than natural cannabinoids. THC is a partial agonist, whilst synthetic cannabinoids are full agonists (Zaleta et al., 2016), producing an effect four to five times stronger than natural marijuana (Wells et al., 2011).
- As synthetic cannabinoids vary in ingredients, they vary in affinity toward either the CB1 or CB2 receptor, producing unpredictable outcomes. A higher affinity toward the CB1 receptor produces more psychotropic effects, including alterations in mood, perceptions, and cognition due to the presence of the receptor in neuronal cells (Alexandre et al., 2020). Whilst having a higher affinity toward the CB1 receptor causes pain relief but reduced psychotropic effects (Alexandre et al., 2020).
CB1 Receptor
edit- The CB1 receptor produces euphoric feelings and psychoactive effects, including alterations in mood, perceptions and cognition (Wells et al., 2011; Alexandre et al., 2020). The receptors exist in neuronal cells within the brain, densely packed in the prefrontal cortex and the hippocampus, within the central nervous system, connective tissue, glands, organs, and gonads (Fantegrossi et al., 2018; Alexandre et al., 2020; Samaan et al., 2016). The location of these receptors explains why users experience nausea relief and a sense of euphoria (Samaan et al., 2016). The binding of the CB1 receptors inhibits the release of hormones including acetylcholine, noradrenaline, GABA and glutamate, altering brain functions including memory, cognition, motor cognition, and autonomic functioning (Alexandre et al., 2020).
CB2 Receptor
edit- The CB2 receptor is responsible for mood regulation, behavior regulation, and pain control, as the receptors are located in the immune system, nervous system, and gastrointestinal system (Fantegrossi et al., 2018; Wells et al., 2011). The CB2 receptor regulates the immune system and central nervous system as they are densely located in immune cells (Alexandre et al., 2020). The synthetic cannabinoids interact with the CB2 receptor, causing 2-Arachidonoylglycerol, an agonist to activate the CB2 receptors located in the brainstem to produce effects in the nervous system (Samaan et al., 2016). The cannabinoid interaction with the nervous system produces the pain relief that users experience after intoxication. The increased activity in the central nervous system can also cause agitation, explaining why users experience confusion or delusions (Samaan et al., 2016).
Hangover
edit- Lana’s symptoms of exhaustion and feeling sluggish are characterized by the ‘hangover’ period of using synthetic cannabis. This period causes users to feel dull, tired, monotonous, and dehydrated. (Akram et al., 2019). Users often develop a dependence to smoking synthetic cannabis to avoid this feeling.
- Users experience a zombie-like, emotionally numb state characterized by feelings of apathy and disconnect from reality. The constant feeling of depersonalization causes life to feel mundane, resulting in users losing interest in the things they normally would enjoy (Soussan et al., 2014).
- Research is limited in determining the cause of the hangover period but findings are consistent in multiple clinical case studies.
“It’s like losing the magic of life, the thing that makes me feel animated, soulful and having a personality.”
"The next day I feel lobotomized, and nothing is fun or boring.”
Comments from individuals who experienced the hangover period (Soussan et al., 2014)
Case Study Part 1: Quiz
What receptor is responsible for Lana feeling happy? 1. The CB1 receptor 2. The CB2 receptor |
Answer
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1. Correct
2. Incorrect The CB1 receptor produces the happy feelings and psychoactive effects from the synthetic marijuana (Wells et al., 2011). |
Memory Problems and Synthetic Cannabinoids
editLong-term use of synthetic cannabinoids results in short-term and long-term disruptions in memory retention (Cohen et al., 2017).
Case Study Part 2: Memory Problems
After smoking for four months, Lana has trouble remembering things, this interferes with her daily life as she cannot remember important events or recall the things she would do. Lana often feels confused and is not able to distinguish what is real and what is not, she is delusional and disorganized (Soussan et al., 2014) |
- Chronic use of synthetic cannabinoids causes volume reductions and disruptions in the hippocampus, disrupting short-term and long-term memory retention (Wells, 2011; Cohen et al., 2017). Synthetic cannabinoids are agonists to the CB1 receptors located in the hippocampus, causing impairments in synaptic plasticity, and therefore, memory processes (Cohen et al., 2017). This explains Lana's inability to recall her memories.
- The hippocampus is responsible for encoding and acquiring new information. The new information is manipulated by the working memory system within the prefrontal cortex. Synthetic cannabinoids have deleterious effects, directly reducing hippocampal encoding ability, therefore, reducing input relay to the prefrontal cortex. This causes disruptions within the working memory system (Cohen et al., 2017).
- As the working memory system is responsible for complex cognitive tasks such as learning, comprehension, and stores and processes information, this can explain why Lana is having problems recalling her short-term memories and is delusional as her cognitive ability is negatively impacted.
- Synthetic cannabinoid abuse also affects the insula, anterior cingulate cortex, precuneus, inferior frontal gyrus, frontal orbital gyrus, and middle frontal gyrus. The functional and structural changes in these brain regions are responsible for the emotional disturbances in users, inducing feelings of confusion, loss, and feeling fragmented (Soussan et al., 2014).
“I tried watching Family Guy during intoxication, but the whole time I forgot what the episode was about.” (Soussan et al., 2014).
Users experience difficulties concentrating after consumption of synthetic cannabis, which can induce feelings of frustration (Soussan et al., 2014).
Case Study Part 2 Quiz: Memory Loss
Why is Lana experiencing memory loss? 1. The synthetic cannabinoids interact with the amygdala causing disruptions in memory retention 2. The synthetic cannabinoids interact with the hippocampus causing disruptions in memory retention |
Answer
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1. Incorrect
2. Correct The hippocampus is responsible for storing and processing new information, therefore, the interaction of synthetic cannabis disrupts normal functioning, resulting in memory problems (Cohen et al., 2017).|}Synthetic Cannabinoids and DepressioneditChronic use of synthetic cannabinoids increases the risk of developing depression (Cohen et al., 2017).
Emotionally numbedit‘The drug-totally distorted my personality, it turned me inside out… it made me blunt, and switched off my brain’ (Akram et al., 2019) Mood changesedit‘When I smoked I was wallowing in self-pity, I felt sorry for myself, I was alone, I didn’t care about anybody else, I hated everyone (Akram et al., 2019)
Synthetic Cannabinoids Cause Cardiac Problems and PsychosiseditChronic and long-term synthetic cannabinoid abuse is correlated with cardiac problems including tachycardia, and psychotic problems leading to the development of psychosis (Fantegrossi et al., 2018; Soussan et al., 2014).
Psychosisedit
Tachycardiaedit“There was a bolt of lightning in the body and my heart started racing like I was having a heart attack.” (Soussan et al., 2014).
Synthetic Cannabinoids - Dependence and WithdrawaleditLong term abuse of synthetic cannabinoids causes a strong dependence, producing withdrawal symptoms that negatively impact quality of life and mental health (Soussan et al., 2014).
As the chemical formulations of synthetic cannabinoid mixes vary, binding affinity to the CB1 and CB2 receptors vary, producing unpredictable symptoms (Alexandre et al., 2020). Users can experience a combination of the following symptoms depending on their dose and previous usage (Alexandre et al., 2020).
ConclusioneditSynthetic cannabinoids are a human-made drug that replicates the feeling of natural cannabis (Byard & Payne-James, 2015). Consumption of synthetic cannabinoids results in adverse psychical, behavioral, cognitive, and psychosocial symptoms determined by the binding affinity to the CB1 and CB2 receptors (Samaan et al., 2016). Research literature concludes that intoxication warrants euphoric feelings due to the CB1 receptor. Short-term and long-term memory problems occur, causing individuals to experience confusion due to disruptions in the hippocampus (Cohen et al., 2017). Synthetic cannabis causes users to experience depression and delusions due to decreased serotonin levels (Cohen et al., 2017). Psychosis manifests in chronic synthetic cannabis users due to the interactions with dopamine receptors (Fantegrossi et al., 2018). Users often experience tachycardia to the cannabinoid interaction with the CB1 receptor, promoting atheroma formations (Zaleta et al., 2016). Synthetic cannabis is addictive and withdrawal is characterized by depression, suicidal thoughts, and urges to consume other drugs (Soussan et al., 2014). Synthetic cannabis causes unpredictable emotional, physical, cognitive, and psycho-social symptoms, thus the conclusion is it should be avoided and not consumed (Millis et al., 2018). See Alsoedit
ReferenceseditAkram, H., Mokrysz, C., & Curran, H. V. (2019). What are the psychological effects of using synthetic cannabinoids? A systematic review. Journal of Psychopharmacology, 33(3), 271–283. https://doi.org/10.1177/0269881119826592
Alexandre, J., Carmo, H., Carvalho, F., & Silva, J. P. (2020). Synthetic cannabinoids and their impact on neurodevelopmental processes. Addiction biology, 25(2), e12824. https://doi.org/10.1111/adb.12824 Baddeley, A. (1992). Working memory. Science, 255(5044), 556-559. https://doi.org/10.1126/science.1736359 Byard, R., & Payne-James, J. (2015). Encyclopedia of forensic and legal medicine. Academic Press. https://doi.org/10.1007/s00414-005-0067-5 Cohen, K., Kapitány-Fövény, M., Mama, Y., Arieli, M., Rosca, P., Demetrovics, Z., & Weinstein, A. (2017). The effects of synthetic cannabinoids on executive function. Psychopharmacology, 234(7), 1121-1134. https://doi.org/10.1007/s00213-017-4546-4 Cohen, K., Mama, Y., Rosca, P., Pinhasov, A., & Weinstein, A. (2020). Chronic use of synthetic cannabinoids is associated with impairment in working memory and mental flexibility. Frontiers in psychiatry, 11, 602. https://doi.org/10.3389/fpsyt.2020.00602 Cottencin, O., Rolland, B., & Karila, L. (2014). New designer drugs (synthetic cannabinoids and synthetic cathinones): review of literature. Current pharmaceutical design, 20(25), 4106-4111. https://doi.org/10.2174/13816128113199990622 Hoyte, C. O., Jacob, J., Monte, A. A., Al-Jumaan, M., Bronstein, A. C., & Heard, K. J. (2012). A characterization of synthetic cannabinoid exposures reported to the National Poison Data System in 2010. Annals of emergency medicine, 60(4), 435-438. https://doi.org/10.1016/j.annemergmed.2012.03.007 Mills, B., Dishner, E., & Velasco, C. E. (2018, April). Acute myocardial infarction triggered by use of synthetic cannabis. In Baylor University Medical Center Proceedings (Vol. 31, No. 2, pp. 200-202). Taylor & Francis. https://doi.org/10.1080/08998280.2017.1416243 Soussan, C., & Kjellgren, A. (2014). The Flip Side of “Spice”: The Adverse Effects of Synthetic Cannabinoids as Discussed on a Swedish Internet Forum. Nordic Studies on Alcohol and Drugs, 31(2), 207–220. https://doi.org/10.2478/nsad-2014-0016 Sutcliffe, O. Ralphs, R. (2018). What is Spice and why is the drug so dangerous? https://theconversation.com/what-is-spice-and-why-is-the-drug-so-dangerous-60600 Synthetic Marijuana Abuse & Addiction Effects, Signs & Symptoms. (2021). Mount Regis Center. https://www.mtregis.com/addiction/synthetic-marijuana/effects-signs-symptoms/ Wells DL, Ott CA. The “New” Marijuana. Annals of Pharmacotherapy. 2011;45(3):414-417. https://doi.org/10.1345/aph.1P580 Winstock, A. R., & Barratt, M. J. (2013). Synthetic cannabis: a comparison of patterns of use and effect profile with natural cannabis in a large global sample. Drug and alcohol dependence, 131(1-2), 106-111. https://doi.org/10.1016/j.drugalcdep.2012.12.011 Zaleta, S., Kumar, P., & Miller, S. (2016). Chest pain, troponin rise, and ST-elevation in an adolescent boy following the use of the synthetic cannabis product K2. Annals of pediatric cardiology, 9(1), 79. https://doi.org/10.4103/0974-2069.171400 External linksedit
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